Table of Contents  
INVITED RESEARCH HIGHLIGHT
Year : 2015  |  Volume : 17  |  Issue : 4  |  Page : 574-582

Remodeling of the plasma membrane in preparation for sperm-egg recognition: roles of acrosomal proteins


1 Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa; Department of Obstetrics and Gynaecology, University of Ottawa; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada
2 Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada
3 Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Anatomy, Faculty of Medical Sciences, Naresuan University, Phitsanulok, Thailand
4 Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
5 Chronic Disease Program, Ottawa Hospital Research Institute; Division of Infectious Diseases, Ottawa Hospital - General Campus, Ottawa, Ontario, Canada;
6 Pasarow Mass Spectrometry Laboratory, University of California, Los Angeles, California, USA
7 The ARC Centre of Excellence in Biotechnology and Development, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia
8 Department of Cell Biology and Biochemistry, Health Sciences Center, Texas Tech University, Texas, USA
9 Department of Animal Science, University of California, Davis, California, USA

Date of Web Publication18-May-2015

Correspondence Address:
Nongnuj Tanphaichitr
Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa; Department of Obstetrics and Gynaecology, University of Ottawa; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1008-682X.152817

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  Abstract 

The interaction of sperm with the egg's extracellular matrix, the zona pellucida (ZP) is the first step of the union between male and female gametes. The molecular mechanisms of this process have been studied for the past six decades with the results obtained being both interesting and confusing. In this article, we describe our recent work, which attempts to address two lines of questions from previous studies. First, because there are numerous ZP binding proteins reported by various researchers, how do these proteins act together in sperm-ZP interaction? Second, why do a number of acrosomal proteins have ZP affinity? Are they involved mainly in the initial sperm-ZP binding or rather in anchoring acrosome reacting/reacted spermatozoa to the ZP? Our studies reveal that a number of ZP binding proteins and chaperones, extracted from the anterior sperm head plasma membrane, coexist as high molecular weight (HMW) complexes, and that these complexes in capacitated spermatozoa have preferential ability to bind to the ZP. Zonadhesin (ZAN), known as an acrosomal protein with ZP affinity, is one of these proteins in the HMW complexes. Immunoprecipitation indicates that ZAN interacts with other acrosomal proteins, proacrosin/acrosin and sp32 (ACRBP), also present in the HMW complexes. Immunodetection of ZAN and proacrosin/acrosin on spermatozoa further indicates that both proteins traffic to the sperm head surface during capacitation where the sperm acrosomal matrix is still intact, and therefore they are likely involved in the initial sperm-ZP binding step.


How to cite this article:
Tanphaichitr N, Kongmanas K, Kruevaisayawan H, Saewu A, Sugeng C, Fernandes J, Souda P, Angel JB, Faull KF, Aitken R J, Whitelegge J, Hardy D, Berger T, Baker M. Remodeling of the plasma membrane in preparation for sperm-egg recognition: roles of acrosomal proteins. Asian J Androl 2015;17:574-82

How to cite this URL:
Tanphaichitr N, Kongmanas K, Kruevaisayawan H, Saewu A, Sugeng C, Fernandes J, Souda P, Angel JB, Faull KF, Aitken R J, Whitelegge J, Hardy D, Berger T, Baker M. Remodeling of the plasma membrane in preparation for sperm-egg recognition: roles of acrosomal proteins. Asian J Androl [serial online] 2015 [cited 2019 Oct 22];17:574-82. Available from: http://www.ajandrology.com/text.asp?2015/17/4/574/152817 - DOI: 10.4103/1008-682X.152817


  Sperm Capacitation and Sperm-Zona Pellucida Interaction- Background and Confusion in the Fields Top


Sperm capacitation was first described by Chang to be a physiological process occurring in the female reproductive tract whereby spermatozoa gain fertilizing ability. [1],[2] Subsequent studies indicate that capacitation can be induced in vitro simply by incubating spermatozoa in a medium containing albumin, calcium and bicarbonate. [3],[4],[5],[6],[7] The procedures of in vitro capacitation and egg culture were then combined to establish the in vitro fertilization process, which is now used routinely as part of assisted reproductive technology. [8] On the research side, the ability to induce sperm capacitation in vitro has also accelerated studies on the molecular mechanisms of the process. Hyperactivated motility patterns are now known as signature movements of capacitated (Cap) sperm. Increases in sperm tyrosine phosphorylation are other emblems of capacitation-associated signaling events. [9]

Remodeling of the molecular components on the sperm surface is another capacitation-associated event that has unfolded from research from the past few decades. Albumin and high-density lipoproteins present in the female reproductive tract or medium induce the release of cholesterol from the sperm surface during capacitation, thus leading to an enhancement in sperm membrane fluidity. [10],[11] This can be detected by a fluorescent dye, merocyanine, which intercalates into the disorganized membrane domains. [7],[12],[13] This increase in membrane fluidity prepares Cap sperm for the downstream membrane fusion events that are essential for fertilizing ability, that is, the acrosome reaction and sperm-egg plasma membrane fusion. [9]

The ability to culture spermatozoa and eggs in vitro has also allowed researchers to identify a number of proteins that are involved in sperm-zona pellucida (ZP) interaction. With success in the purification of the three mouse (m) ZP glycoproteins to homogeneity, Florman and Wassarman confirmed that the mZP3 glycoprotein was a primary receptor binding to acrosome intact sperm, whereas mZP2 was a secondary receptor engaging in adhering acrosome reacted sperm to the ZP. [14] This concept was later questioned by Gerton et al. who showed that acrosomal exocytosis occurs in a gradual manner [15],[16],[17] and that both mZP2 and mZP3 engage in the interaction with sperm undergoing acrosomal exocytosis. Recent work of Dean et al. further indicated that mZP2 cannot be excluded from the binding of acrosome-intact sperm. [18],[19] The assumption that mZP3 binds only to acrosome intact spermatozoa has also been recently challenged by Hirohashi's research group, who showed using high-performance videomicroscopy that acrosomal exocytosis has already initiated by the time that sperm have moved through the cumulus cell layers. [20] In other words, spermatozoa that bind to the ZP do not have their acrosome completely intact. Regardless of this confusion, one finding that still holds true is that ZP glycoproteins are endowed with large carbohydrate moieties and that ZP glycans are important in the initial binding of the ZP to spermatozoa. [9]

On the sperm side, the membrane β-1,4-galactosyltransferase (GalT) is one of the early proteins described by Shur and Hall for its affinity for the ZP and its involvement in sperm-ZP binding was described through a series of in vitro experiments. [21],[22],[23],[24] Shur et al. have hypothesized that GalT is engaged in a "dead-end" reaction. Normally, GalT transfers a galactose from a galactose donor (UDP-Gal) to N-acetylglucosamine (GlcNAc) to form a Gal-GlcNAc conjugate. In the female reproductive tract, Shur and Hall have suggested that UDP-Gal was not present and, therefore, the binding of sperm GalT to its substrate GlcNAc on the ZP glycans forms a basis of sperm-ZP interaction without yielding a product. [21],[22] The same "dead-end reaction" concept can be applied to a number of sperm surface glyco-enzymes with ZP affinity: namely that they bind to their substrate, which contains a sugar residue present on the ZP glycans. These enzymes include α-D-mannosidase, [25],[26] PH-20 (aka SPAM1), [27],[28] arylsulfatase A (ARSA, with galactose sulfate as one of its substrates). [29],[30] Considering that these glycol-enzymes do not complete their reaction at the time of sperm-ZP binding, they can be considered as "lectins." However, it is possible that the reaction of these enzymes is eventually completed, so that sperm can leave the original binding site and move to the next one, as part of their forward movement through the ZP.

Besides the glycol-enzymes, there exists another set of sperm surface proteins with a direct lectin property. These include proacrosin/acrosin (ACRO), [31],[32] sp56 (aka ZP3R), [33] sp38 (aka IAM38, ZP binding protein1 [ZPBP1]), [34],[35],[36] zonadhesin (ZAN), [37],[38] sp17 [39] and spermadhesins (including AQN, AWN). [40],[41],[42] In addition, ZP binding proteins on the sperm surface without known information for their ability to interact with the carbohydrate moieties of the ZP have been described, including SED1 (aka MFGM), [43] ZP binding protein2 (ZPBP2), [44] glutathione-S-transferase; [45] ADAM3, [46] carbonyl reductase, [47] basigin, [48] SP10 [49] and FA-1. [50],[51] Sulfogalactosylglycerolipid (SGG, aka seminolipid) [52],[53] is another sperm surface molecule (not a protein) that has affinity for the ZP and is involved in sperm-ZP binding. Of note is the acrosomal location of a number of ZP binding proteins: that is, proacrosin/acrosin, ZAN, ZPBP1, ZPBP2, SP10, and sp56, [35],[36],[38],[44],[54],[55],[56],[57],[58],[59],[60],[61] and this finding reinforces the concept that these ZP binding proteins are involved in the binding of the reacting acrosome to the ZP. However, before the results described by Jin et al. [20] it was thought that the acrosomal exocytosis occurred on the ZP and that the binding of these acrosomal proteins to the ZP occurred after the initial binding of ZP-associated proteins on the sperm head surface. As described below, this concept is now challenged by our recent results.


  Why are There so Many Zona Pellucida Binding Proteins? Top


The existence of so many sperm proteins with ZP affinity requires an explanation. One possible explanation is that information derived from the in vitro sperm-ZP binding assay does not accurately represent situations in vivo. With the rapidly advancing technology of targeted gene deletion (see http://www.genome.gov/12514551), colonies of "knockout" (KO) mice lacking individual genes encoding ZP binding proteins have been produced and fecundity of these male mice was assessed by various measurements that is, their ability to sire offspring, their sperm parameters (sperm number, motility, morphology and in vitro fertilizing ability), and their libido and ability to copulate with females. [62] Surprisingly and interestingly, a number of KO mice including Gal−/−, Zp3r−/−, Zan−/−, SED1−/−, Acr−/−, Zpbp2−/−, Spam1−/− and Arsa−/− mice can sire offspring, [43],[44],[63],[64],[65],[66],[67],[68],[69] although evidence of subfertility is noted in a number of these mouse colonies. [43],[44],[69],[70] In contrast, Adam3−/− and Zpbp1−/− mice, which still produce spermatozoa, are infertile. [44],[46],[71],[72] Of note, ADAM3 also functions in sperm-egg plasma membrane binding. [72] While spermatozoa from Adam3−/− mice lack ADAM3, as expected, they also possess an aberrant amount of proteins that are important for sperm-egg plasma membrane binding on their surface (i.e. no ADAM1b and a lower amount of ADAM2). [72] In addition, spermatozoa from Adam3−/− mice are severely defective in their movement through the uterotubal junction. [71] All of these observations indicate the multi-functional roles of ADAM3 in fertilization and it is therefore not surprising that Adam3−/− male mice are infertile. In the same vein, spermatozoa from Zpbp1−/− mice have grossly abnormal heads (typical of the so-called "globospermia" morphology), suggesting that ZPBP1 is involved in the formation of the sperm acrosome. [44] The infertility status of Zpbp1−/− mice is, therefore, to be expected.

Explanations are required for the existence of so many sperm proteins with ZP affinity in the first category, the deletion of whose genes still produces fertile male mice (see above). The results from these KO mouse studies indicate that these proteins are not essential for fecundity, although their relevance in the ZP binding process cannot be denied (especially when a number of these KO male mice are subfertile). Because fertilization is the fundamental process needed to sustain the continuation of a species, a number of ZP binding proteins/molecules may be required to safeguard this. The redundancy of their functions would allow them to back up for one another. Alternatively, they might act together in a synergistic and/or sequential manner, although the disappearance of one specific molecule does not annul the sperm-ZP binding process. [73],[74],[75]


  Existence of Zona Pellucida Binding Proteins/Molecules in Sperm Lipid Rafts and High Molecular Weight Complexes Top


The interpretation of the presence of many ZP binding proteins/molecules on sperm is consistent with the concept of the existence of lipid rafts, nanoscale liquid-ordered sterol-containing membrane microdomains that are platforms of cell adhesion and signaling molecules. [73],[76],[77],[78] The method to isolate lipid rafts as detergent resistant membranes (DRMs) [79] has further accelerated the characterizations of their molecular components, results of which have supported the stated concept. Since sperm-egg interaction is fundamentally engaging cell adhesion and signaling processes, a number of investigators in the gamete field, including us, started to characterize sperm lipid rafts. So far, publications on the sperm lipid rafts topic have come out from at least 17 labs, [78] starting with the article from Kitajima's lab [80] describing the ability of sea urchin sperm DRMs to bind to a sperm binding protein on the egg. Likewise, we have shown that pig and mouse sperm DRMs have affinity for homologous ZP glycoproteins and the intact ZP, respectively. [81],[82] Our results showing a higher amount and enhanced ZP binding ability of DRMs isolated from Cap sperm as compared with those from noncapacitated (Noncap) spermatozoa further support the concept that sperm lipid rafts are the ZP interaction domains on the sperm surface. [81] Our lipidomic characterization further indicated that SGG is an integral component of sperm DRM: it plays an important role in the formation of sperm lipid rafts as well as endowing their ZP binding ability. Proteomic analyses further revealed the presence of a number of ZP binding proteins (SED1, GalT, α-D-mannosidase, SPAM1, ARSA, spermadhesins, basigin, proacrosin, SP10) as well as their associated partners (e.g, sp32 or ACRBP) as molecular components of sperm DRMs. [82],[83],[84] Significantly, these findings imply that these ZP binding proteins have to be escorted into the lipid raft domains. Therefore, it is not surprising that several chaperone proteins are also present in isolated sperm DRMs including a series of heat shock proteins (e.g, Hsp60 (chaperonin), HspA5, and Hsp90, Hsp90b1 (endoplasmin)), calnexin, protein disulfide isomerase associated 3 and protein disulfide isomerase associated 6. [82] The co-existence of ZP binding proteins and chaperone proteins in isolated sperm lipid rafts suggests that they must be in close proximity and might be associated with one another forming high molecular weight (HMW) complexes within the lipid raft microdomains. This postulate was indeed verified by Dun et al. Blue native gel electrophoresis of proteins extracted from whole sperm with a gentle nonionic detergent reveals the presence of HMW complexes, which have affinity for solubilized ZP glycoproteins. In mouse spermatozoa, ZPBP2, ZPBP1, and ZP3R and a series of chaperone proteins, chaperonin-containing TCP complex (CCT/TRiC) are molecular constituents of a 820 kDa HMW complex. [85] A similar type of HMW protein complex (~900 kDa) is also present in human spermatozoa, although ZPBP2 is the only ZP binding protein constituent. [86] A smaller HMW complex (200 kDa) is also present in human sperm comprising two ZP binding proteins, ARSA and SPAM1, and a chaperone protein, HspA2. [87] Of note, only a few ZP binding proteins are found in the sperm HMW complexes with ZP affinity. It is possible that proteins extracted from other regions of spermatozoa besides the anterior head (site of ZP binding) may have diluted out HMW complexes that are directly involved in ZP interaction: this dilution would make it difficult technically to detect these relevant complexes.


  Proteomic Characterization of Sperm Anterior Head Plasma Membrane Vesicles - Existence OF High Molecular Weight Complexes with Zona Pellucida Affinity Top


Toward the end of the 2000's, concerns over the use of detergents to isolate lipid rafts were voiced strongly; DRMs can be artifacts from protein aggregation induced by this treatment. [88] Isolation of lipid rafts by physical force such as nitrogen cavitation was suggested. [89] In fact, in the sperm biology field, nitrogen cavitation at 650 psi has been used since the 1980's to specifically prepare vesicles from the pig sperm anterior head plasma membrane (APM), the site of ZP binding. [90],[91] Isolated APM vesicles from Cap pig sperm have a direct ability to bind to the homologous ZP glycoproteins with the same Kd value as that measured for Cap sperm DRMs for the parallel ZP interaction. [81] Therefore, we started our proteomic characterization of APM vesicles isolated from Noncap and Cap sperm, with the hope of gaining an insight to the identities of proteins that are relevant in capacitation. Our recent results indicate that the amount of APM vesicles isolated from Cap sperm increased to 160% compared with that from Noncap sperm, and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) also indicated an increase in the protein numbers in Cap APM vesicles (127 vs 81 in Noncap APM vesicles, with 59 proteins found in common between Noncap and Cap vesicles). Significantly, a number of proteins involved in sperm-egg interaction and two chaperone proteins (heat shock 70 kDa protein 1-like and heat shock protein Hsp90-alpha) rank the highest in their spectral counts among all proteins identified by LC-MS/MS [Table 1]. The presence of ZP binding proteins in APM vesicles corroborates their known ZP binding properties [81],[92] and the increase in the amounts of isolated APM vesicles in Cap sperm further explains the higher capacity of these sperm (compared with Noncap counterparts) for ZP interaction. [93]
Table 1: LC-MS/MS analyses of Noncap and Cap APM vesicle proteinsa,b


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Blue native gel electrophoresis further revealed the presence of HMW protein complexes (>200 kDa) in APM vesicles from Noncap and Cap sperm ([Figure 1]a, left panel ), but HMW complexes sized 1000-1300 kDa (named Complex I), 850-1000 kDa (Complex II) and 750-850 kDa (Complex III) from Cap sperm had a significantly higher capacity to bind to pig ZP3 glycoproteins (hetero-oligomers of pig ZP3α and pig ZP3β; sperm receptor; [Figure 1]a, right panel ). As expected, LC-MS/MS revealed that proteins known for their affinity for the ZP scored the highest for the spectral counts in all three complexes and the amounts of most of these proteins were higher in Cap HMW complexes ([Figure 1]d). Interestingly, ZAN had the highest spectral counts in the three complexes. This finding was in contrast to the LC-MS/MS results of the whole APM vesicle extracts where SED1 scored the highest in spectral counts and ZAN the lowest in the protein category of sperm-egg interaction [Table 1]. The presence of ZAN in Complexes I, II and III was confirmed by immunoblotting ([Figure 1]b ). The anti-ZAN reactive bands in the three complexes corresponded to the pig ZP3 binding patterns ([Figure 1]a). Significantly, ZAN contributed to the ZP affinity of the three complexes. Preincubation of the complexes with various concentrations of anti-ZAN IgG inhibited their binding to pig ZP3 in a dose-dependent manner ([Figure 1]c ).
Figure 1: ( a ) Left panel: Presence of HMW complexes in pig APM vesicles as shown by blue native gel electrophoresis/silver staining; Right panel: Far western blotting showing the binding of Complex I (1000-1300 kDa), Complex II (850-1000 kDa) and Complex III (750-850 kDa) to biotinylated pig ZP3 (sperm receptor). ( b ) Immunoblotting of Cap sperm APM proteins separated by blue native gel electrophoresis, showing zonadhesin bands in the three Complexes with patterns similar to the far western bands of ZP3 binding. ( c ) Preincubation of APM Complexes with anti-zonadhesin (anti-ZAN) IgG inhibits the Complex binding to ZP3 in a dose dependent manner. ( d ) Identity and spectral counts of proteins in the three HMW Complexes. For experimental details of results described throughout this article, see Kongmanas et al.93. All figures shown in this review are also adapted from this article.

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Chaperones are also present in Complexes I-III, including various subunits of T-complex protein 1 (aka CCT/TRiC). [93] As suggested earlier by Dun et al. [85],[86],[87] these chaperones might escort the ZP binding proteins to come together to form HMW complexes.


  Zonadhesin and Selective Acrosomal Proteins Play Roles in Sperm Capacitation Top


Besides ZAN, proacrosin, ACRBP, SP10 and ZPBP1 are ZP binding proteins present in the three HMW complexes ([Figure 1]d ). All of these proteins are known to localize in the acrosome. Previous studies indicated that vesicles of hybrid membranes (APM and outer acrosomal membrane) existed in the vesicle preparation from pig sperm subjected to nitrogen cavitation at 650 psi (called APM vesicles in this review). [94] ZAN was localized to the outer acrosomal membrane and acrosomal matrix. [38],[57] Therefore, its existence as revealed by LC-MS/MS in the HMW complexes might reflect these previous findings. The question relevant to the physiology of sperm-ZP interaction, however, remains: are acrosomal proteins present in the APM HMW complexes exposed on the sperm head surface, so that they can bind to the ZP? Our immunofluorescence and flow cytometry of ZAN on intact pig sperm indeed revealed that ZAN was not present on the head surface in the majority of spermatozoa resuspended in medium that did not support capacitation. However, the percentage of sperm that were positively labeled with anti-ZAN increased when sperm were incubated in capacitating medium (containing albumin, bicarbonate, and CaCl 2 ) for 30 min ([Figure 2]a). In addition, the immunofluorescence intensity of ZAN increased in these spermatozoa. Both the percentage of anti-ZAN labeled sperm and the immunofluorescence intensity peaked at 60 min incubation in capacitating medium ([Figure 2]b). However, most spermatozoa (≥80%) were still acrosome-intact as shown by the binding of FITC-labeled Pisum sativum agglutinin to their acrosomal matrix ([Figure 2]b). Corroborating this result is the observation that ZAN remained in the acrosome of nitrogen-cavitated spermatozoa with a much higher level of immunofluorescence intensity than that present on the head surface of the corresponding Cap acrosome-intact sperm ([Figure 2]c). All of these results indicate that a fraction of ZAN is transported from the acrosome to the sperm head surface during capacitation. Immunofluorescence and flow cytometry of proacrosin/acrosin show the same trend as ZAN in terms of their transport to the sperm head surface. [93] However, the transportation of ACRBP (sp32) to the sperm head surface appeared to be much earlier than that of ZAN and proacrosin/acrosin. ACRBP was present on the head surface of almost all Noncap spermatozoa and this distribution remained the same when sperm were incubated in capacitating medium, although the intensity of the immunofluorescence increased slightly. ACRBP possesses a specific affinity to proacrosin (53 kDa) but not to the intermediate and mature forms of acrosin (43 and 35 kDa, respectively). All of these proacrosin/acrosin forms are present in Noncap and Cap spermatozoa. Therefore, the overall results suggest that ACRBP targets to the head surface of Noncap sperm independently of proacrosin. While the transport of ZAN and proacrosin (both with known ZP affinity) to the APM region of Cap sperm is likely beneficial for interaction with the ZP, the benefit of having ACRBP is still a matter of investigation. To date, direct affinity of ACRBP for the ZP has not been demonstrated.
Figure 2: ( a and b ) Zan targets to the pig sperm head surface during incubation in capacitating medium. ( a ) Merged immunofluorescence (panels a-d) and phase contrast (panels g-j) images are shown in the left column, whereas the corresponding flow cytometry histograms are shown on the right. Spermatozoa were incubated in capacitating medium for 30 and 60 min. ( b ) Kinetics of the numbers of sperm with ZAN on the head surface is shown as the function of capacitation time, together with the population of acrosome reacted sperm (negatively stained with PSA). ( c ) Immunofluorescence and flow cytometry indicating that only a fraction of ZAN was targeted to the sperm surface and that most of the protein remained in the acrosome of nitrogen cavitated sperm. ( d ) Immunofluorescence of SED1 (MFGM) on spermatozoa before and after nitrogen cavitation. Results indicate the same fluorescence pattern/intensity of SED1 in Noncap and Cap sperm and the absence of the protein in the acrosome of nitrogen-cavitated gametes. Zan: zonadhesin; Noncap: noncapacitated; Cap: capacitated; PSA: pisum sativum agglutinin.

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As with ACRBP, the presence of SED1 before and after capacitation was of similar pattern and intensity ([Figure 2]d ). This result is not surprising, because SED1 is secreted by epididymal epithelial cells into the lumen and is deposited onto the sperm head surface during passage through the epididymis. [43] The absence of SED1 in the acrosome of nitrogen cavitated sperm supports the idea that SED1 is acquired externally during epididymal maturation. The ZP affinity of SED1 would contribute to the baseline ZP interactions by HMW complexes of Noncap sperm ([Figure 1]a ).

Zonadhesin is a mosaic protein comprising a number of cell adhesion-related domains (MAM, mucin, and von Willebrand factor D [VWF D]) ([([Figure 3]a ). It is synthesized in spermatids as a precursor protein and then processed to mature forms p45 and p105, present in mature spermatozoa. [37] Both p45 and p105 still contain VWF D domains: VWF D1 + D2 in p45 and VWF D2 + D3 + D4 in p105. These VWF D domains are likely the basis for the ZP affinity of p45 + p105, as well as their multimerization and interactions with other proteins. [37],[38] Even on SDS-PAGE, HMW forms of Zan (300-500 kDa and higher) are present along with p45 and p105 mature forms, [37] a result that corroborates the presence of ZAN using blue native gel electrophoresis [Figure 1]. With this molecular adhesion property, ZAN might interact with other acrosomal proteins, scaffolding them as HMW complexes for transport to the sperm APM. In fact, our immunoprecipitation results using anti-ZAN IgG captured on paramagnetic beads [93] indicated that ZAN interacts with proacrosin/acrosin and ACRBP in the APM extracts [Figure 3]. However, it is still unclear whether ZAN interacts directly with ACRBP or through the association of ACRBP with proacrosin. On the other hand, ZAN does not interact with SED1 [Figure 3]. This result is not surprising considering that ZAN and SED1 on the sperm surface originate from different sources: ZAN from the acrosome, and SED1 from the epididymal lumen. Regardless, the interaction among the three acrosomal proteins (ZAN, proacrosin/acrosin and ACRBP) would form a basis for their co-existence in the APM complexes, and transportation of a fraction of them to the sperm APM region during capacitation would partially account for the increased amount in isolated APM vesicles in Cap sperm and the higher ZP binding affinity of the Cap gametes. A better understanding of the capacitation process should be gained by unraveling the mechanisms of how ZAN moves to the sperm APM site. ZAN should be the focus in such a protein transport study because it is the main component of the APM HMW complexes with ZP affinity, and transport of ZAN to the sperm head surface is observed in mouse spermatozoa during capacitation. [65] Notably, VWF is known to form multimeric complexes, which are stored intracellularly. However, a soluble fraction of these complexes can be secreted upon the rise of [Ca 2+] i , intracellular cAMP levels and pH i . [95] All of these stimulations take place as part of physiological changes during sperm capacitation, [96],[97] which might possibly trigger the traffic of ZAN to the sperm APM. In addition, the roles of TCP-1 subunits in chaperoning ZAN and other acrosomal proteins to the sperm head surface cannot be ruled out.
Figure 3: ( a ) Structural domains of ZAN (adapted from Bi et al.38 and Herlyn and Zischler.98 ( b ) Immunoprecipitation of APM proteins with anti-ZAN IgG captured on Protein G paramagnetic beads93. Input = whole APM protein extracts; Elute = APM proteins bound to anti-ZAN beads. Results indicate interaction among ZAN, proacrosin/acrosin (ACRO) and ACRBP but not SED1 (MFGM). ZAN: zonadhesin; APM: anterior head plasma membrane.

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  Summary and Perspectives for Our Findings Top


While pig APM vesicles comprise a number of ZP binding proteins and chaperones, only some of these proteins interact with each other to form HMW complexes. ZAN, SED1, proacrosin/acrosin, ACRBP, SP10 and ZPBP1 are the set of proteins in HMW complexes, which are known to be relevant in sperm-ZP binding, whereas TCP-1 subunits are chaperones found in these complexes. HMW complexes from Cap sperm have significantly higher capacity to bind to pig ZP3 glycoproteins (sperm receptors), and this is partly because of the higher amounts of both of these protein constituents, compared with HMW complexes of Noncap sperm. As ZAN, proacrosin/acrosin, ACRBP, ZPBP1 and SP10 are known to be acrosomal proteins, we performed studies with the first three of these to determine whether they are targeted to the sperm head surface during capacitation. Our results revealing that a fraction of ZAN and proacrosin/acrosin indeed traffics to the sperm head surface during capacitation is in accordance with the recent finding in the mouse system that acrosomal exocytosis initiates during sperm migration through the cumulus cell layers: that is, prior to the spermatozoon encountering the ZP. It remains to be seen whether the timing of the inception of acrosomal exocytosis is the same in the pig. Nonetheless, the results suggest that ZAN, proacrosin/acrosin and perhaps also other acrosomal proteins (yet to be identified) that have been trafficked to the sperm head surface are involved in the initial interaction between Cap sperm and the ZP (while the sperm acrosomal matrix still remains relatively intact; see our model in [Figure 4]). The remainder of these acrosomal proteins in the acrosome would then participate in the subsequent interaction of acrosome reacting spermatozoa with the ZP. Moreover, if these proteins move to the inner acrosomal membrane following the completion of acrosomal exocytosis, they might also participate in adhering acrosome-reacted sperm to the ZP. Given that the transport of ZAN to the sperm head surface has also been documented in mouse spermatozoa, [65] the event may be used as a bioindex of sperm capacitation and we have research in progress to determine whether this movement occurs in human spermatozoa. Regardless, this phenomenon should be confirmed in oviductal spermatozoa Cap in vivo, to validate its biological relevance[98].
Figure 4: Proposed model of the involvement of acrosomal proteins in sperm-ZP interaction. During capacitation, a fraction of acrosomal proteins with ZP affinity traffics to the anterior sperm head surface as part of the initiation of acrosomal exocytosis. This endows the ability of Cap sperm to start binding to the ZP. Acrosomal exocytosis continues on the ZP with dispersion of the acrosomal matrix. The same acrosomal proteins in the matrix then contribute to the anchoring of acrosome reacting sperm to the ZP. Key: PM: plasma membrane; OAM: outer acrosomal membrane; IAM: inner acrosomal membrane; ZP: zona pellucida.

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  Author Contributions Top


NT, RJA, MB, DH, TB, KFF, JW and JBA designed the experiments in our research work described in this review. KK, HK, AS, CS, JF and PS performed the lab work. NT, KK and AS prepared the review.


  Competing Interests Top


The authors declare no competing interests.


  Acknowledgments Top


This work was supported by research grants from Canadian Institutes of Health Research (CIHR) and Natural Sciences and Engineering Research Council of Canada (both to NT). KK received a scholarship from the Development and Promotion of Science and Technology Talented Project, Thailand, and by a scholarship from CIHR Strategic Training Initiative in Health Research in Reproduction, Early Development, and the Impact on Health. HK received a postdoctoral fellowship from Naresuan University.

 
  References Top

1.
Chang MC. Fertilizing capacity of spermatozoa deposited into the fallopian tubes. Nature 1951; 168: 697-8.  Back to cited text no. 1
    
2.
Chang MC. The meaning of sperm capacitation. A historical perspective. J Androl 1984; 5: 45-50.  Back to cited text no. 2
    
3.
Davis BK. Timing of fertilization in mammals: sperm cholesterol/phospholipid ratio as a determinant of the capacitation interval. Proc Natl Acad Sci U S A 1981; 78: 7560-4.  Back to cited text no. 3
    
4.
Visconti PE, Bailey JL, Moore GD, Pan D, Olds-Clarke P, et al. Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. Development 1995; 121: 1129-37.  Back to cited text no. 4
    
5.
Visconti PE, Ning X, Fornés MW, Alvarez JG, Stein P, et al. Cholesterol efflux-mediated signal transduction in mammalian sperm: cholesterol release signals an increase in protein tyrosine phosphorylation during mouse sperm capacitation. Dev Biol 1999; 214: 429-43.  Back to cited text no. 5
    
6.
Visconti PE, Krapf D, de la Vega-Beltrán JL, Acevedo JJ, Darszon A. Ion channels, phosphorylation and mammalian sperm capacitation. Asian J Androl 2011; 13: 395-405.  Back to cited text no. 6
    
7.
Harrison RA, Gadella BM. Bicarbonate-induced membrane processing in sperm capacitation. Theriogenology 2005; 63: 342-51.  Back to cited text no. 7
    
8.
Allen VM, Wilson RD, Cheung A, Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), Reproductive Endocrinology Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). Pregnancy outcomes after assisted reproductive technology. J Obstet Gynaecol Can 2006; 28: 220-50.  Back to cited text no. 8
    
9.
Florman HM, Ducibella T. Fertilization in mammals. In: Neill JD, editor. Knobil and Neil's Physiology of Reproduction. New York: Elsevier; 2006. p. 55-112.  Back to cited text no. 9
    
10.
Wolf DE, Hagopian SS, Ishijima S. Changes in sperm plasma membrane lipid diffusibility after hyperactivation during in vitro capacitation in the mouse. J Cell Biol 1986; 102: 1372-7.  Back to cited text no. 10
    
11.
Flesch FM, Gadella BM. Dynamics of the mammalian sperm plasma membrane in the process of fertilization. Biochim Biophys Acta 2000; 1469: 197-235.  Back to cited text no. 11
    
12.
Gadella BM, Harrison RA. The capacitating agent bicarbonate induces protein kinase A-dependent changes in phospholipid transbilayer behavior in the sperm plasma membrane. Development 2000; 127: 2407-20.  Back to cited text no. 12
    
13.
Flesch FM, Brouwers JF, Nievelstein PF, Verkleij AJ, van Golde LM, et al. Bicarbonate stimulated phospholipid scrambling induces cholesterol redistribution and enables cholesterol depletion in the sperm plasma membrane. J Cell Sci 2001; 114: 3543-55.  Back to cited text no. 13
    
14.
Florman HM, Wassarman PM. O-linked oligosaccharides of mouse egg ZP3 account for its sperm receptor activity. Cell 1985; 41: 313-24.  Back to cited text no. 14
    
15.
Kim KS, Gerton GL. Differential release of soluble and matrix components: evidence for intermediate states of secretion during spontaneous acrosomal exocytosis in mouse sperm. Dev Biol 2003; 264: 141-52.  Back to cited text no. 15
    
16.
Buffone MG, Foster JA, Gerton GL. The role of the acrosomal matrix in fertilization. Int J Dev Biol 2008; 52: 511-22.  Back to cited text no. 16
    
17.
Buffone MG, Hirohashi N, Gerton GL. Unresolved questions concerning mammalian sperm acrosomal exocytosis. Biol Reprod 2014; 90: 112.  Back to cited text no. 17
    
18.
Avella MA, Baibakov B, Dean J. A single domain of the ZP2 zona pellucida protein mediates gamete recognition in mice and humans. J Cell Biol 2014; 205: 801-9.  Back to cited text no. 18
    
19.
Gahlay G, Gauthier L, Baibakov B, Epifano O, Dean J. Gamete recognition in mice depends on the cleavage status of an egg's zona pellucida protein. Science 2010; 329: 216-9.  Back to cited text no. 19
    
20.
Jin M, Fujiwara E, Kakiuchi Y, Okabe M, Satouh Y, et al. Most fertilizing mouse spermatozoa begin their acrosome reaction before contact with the zona pellucida during in vitro fertilization. Proc Natl Acad Sci U S A 2011; 108: 4892-6.  Back to cited text no. 20
    
21.
Shur BD, Hall NG. Sperm surface galactosyltransferase activities during in vitro capacitation. J Cell Biol 1982; 95: 567-73.  Back to cited text no. 21
    
22.
Shur BD, Hall NG. A role for mouse sperm surface galactosyltransferase in sperm binding to the egg zona pellucida. J Cell Biol 1982; 95: 574-9.  Back to cited text no. 22
    
23.
Miller DJ, Macek MB, Shur BD. Complementarity between sperm surface beta-1,4-galactosyltransferase and egg-coat ZP3 mediates sperm-egg binding. Nature 1992; 357: 589-93.  Back to cited text no. 23
    
24.
Gong X, Dubois DH, Miller DJ, Shur BD. Activation of a G protein complex by aggregation of beta-1,4-galactosyltransferase on the surface of sperm. Science 1995; 269: 1718-21.  Back to cited text no. 24
    
25.
Tulsiani DR, NagDas SK, Skudlarek MD, Orgebin-Crist MC. Rat sperm plasma membrane mannosidase: localization and evidence for proteolytic processing during epididymal maturation. Dev Biol 1995; 167: 584-95.  Back to cited text no. 25
    
26.
Pereira BM, Abou-Haila A, Tulsiani DR. Rat sperm surface mannosidase is first expressed on the plasma membrane of testicular germ cells. Biol Reprod 1998; 59: 1288-95.  Back to cited text no. 26
    
27.
Primakoff P, Hyatt H, Myles DG. A role for the migrating sperm surface antigen PH-20 in guinea pig sperm binding to the egg zona pellucida. J Cell Biol 1985; 101: 2239-44.  Back to cited text no. 27
    
28.
Hunnicutt GR, Primakoff P, Myles DG. Sperm surface protein PH-20 is bifunctional: one activity is a hyaluronidase and a second, distinct activity is required in secondary sperm-zona binding. Biol Reprod 1996; 55: 80-6.  Back to cited text no. 28
    
29.
Carmona E, Weerachatyanukul W, Soboloff T, Fluharty AL, White D, et al. Arylsulfatase a is present on the pig sperm surface and is involved in sperm-zona pellucida binding. Dev Biol 2002; 247: 182-96.  Back to cited text no. 29
    
30.
Tantibhedhyangkul J, Weerachatyanukul W, Carmona E, Xu H, Anupriwan A, et al. Role of sperm surface arylsulfatase A in mouse sperm-zona pellucida binding. Biol Reprod 2002; 67: 212-9.  Back to cited text no. 30
    
31.
Howes E, Pascall JC, Engel W, Jones R. Interactions between mouse ZP2 glycoprotein and proacrosin; a mechanism for secondary binding of sperm to the zona pellucida during fertilization. J Cell Sci 2001; 114: 4127-36.  Back to cited text no. 31
    
32.
Williams RM, Jones R. Specific binding of sulphated polymers to ram sperm proacrosin. FEBS Lett 1990; 270: 168-72.  Back to cited text no. 32
    
33.
Cheng A, Le T, Palacios M, Bookbinder LH, Wassarman PM, et al. Sperm-egg recognition in the mouse: characterization of sp56, a sperm protein having specific affinity for ZP3. J Cell Biol 1994; 125: 867-78.  Back to cited text no. 33
    
34.
Mori E, Baba T, Iwamatsu A, Mori T. Purification and characterization of a 38-kDa protein, sp38, with zona pellucida-binding property from porcine epididymal sperm. Biochem Biophys Res Commun 1993; 196: 196-202.  Back to cited text no. 34
    
35.
Mori E, Kashiwabara S, Baba T, Inagaki Y, Mori T. Amino acid sequences of porcine Sp38 and proacrosin required for binding to the zona pellucida. Dev Biol 1995; 168: 575-83.  Back to cited text no. 35
    
36.
Yu Y, Xu W, Yi YJ, Sutovsky P, Oko R. The extracellular protein coat of the inner acrosomal membrane is involved in zona pellucida binding and penetration during fertilization: characterization of its most prominent polypeptide (IAM38). Dev Biol 2006; 290: 32-43.  Back to cited text no. 36
    
37.
Hickox JR, Bi M, Hardy DM. Heterogeneous processing and zona pellucida binding activity of pig zonadhesin. J Biol Chem 2001; 276: 41502-9.  Back to cited text no. 37
    
38.
Bi M, Hickox JR, Winfrey VP, Olson GE, Hardy DM. Processing, localization and binding activity of zonadhesin suggest a function in sperm adhesion to the zona pellucida during exocytosis of the acrosome. Biochem J 2003; 375: 477-88.  Back to cited text no. 38
    
39.
Richardson RT, Yamasaki N, O'Rand MG. Sequence of a rabbit sperm zona pellucida binding protein and localization during the acrosome reaction. Dev Biol 1994; 165: 688-701.  Back to cited text no. 39
    
40.
Dostálová Z, Calvete JJ, Sanz L, Töpfer-Petersen E. Boar spermadhesin AWN-1. Oligosaccharide and zona pellucida binding characteristics. Eur J Biochem 1995; 230: 329-36.  Back to cited text no. 40
    
41.
Calvete JJ, Carrera E, Sanz L, Töpfer-Petersen E. Boar spermadhesins AQN-1 and AQN-3: oligosaccharide and zona pellucida binding characteristics. Biol Chem 1996; 377: 521-7.  Back to cited text no. 41
    
42.
Töpfer-Petersen E, Romero A, Varela PF, Ekhlasi-Hundrieser M, Dostàlovà Z, et al. Spermadhesins: a new protein family. Facts, hypotheses and perspectives. Andrologia 1998; 30: 217-24.  Back to cited text no. 42
    
43.
Ensslin MA, Shur BD. Identification of mouse sperm SED1, a bimotif EGF repeat and discoidin-domain protein involved in sperm-egg binding. Cell 2003; 114: 405-17.  Back to cited text no. 43
    
44.
Lin YN, Roy A, Yan W, Burns KH, Matzuk MM. Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Mol Cell Biol 2007; 27: 6794-805.  Back to cited text no. 44
    
45.
Hemachand T, Gopalakrishnan B, Salunke DM, Totey SM, Shaha C. Sperm plasma-membrane-associated glutathione S-transferases as gamete recognition molecules. J Cell Sci 2002; 115: 2053-65.  Back to cited text no. 45
    
46.
Shamsadin R, Adham IM, Nayernia K, Heinlein UA, Oberwinkler H, et al. Male mice deficient for germ-cell cyritestin are infertile. Biol Reprod 1999; 61: 1445-51.  Back to cited text no. 46
    
47.
Boué F, Bérubé B, De Lamirande E, Gagnon C, Sullivan R. Human sperm-zona pellucida interaction is inhibited by an antiserum against a hamster sperm protein. Biol Reprod 1994; 51: 577-87.  Back to cited text no. 47
    
48.
Saxena DK, Oh-Oka T, Kadomatsu K, Muramatsu T, Toshimori K. Behaviour of a sperm surface transmembrane glycoprotein basigin during epididymal maturation and its role in fertilization in mice. Reproduction 2002; 123: 435-44.  Back to cited text no. 48
    
49.
Coonrod SA, Herr JC, Westhusin ME. Inhibition of bovine fertilization in vitro by antibodies to SP-10. J Reprod Fertil 1996; 107: 287-97.  Back to cited text no. 49
    
50.
Naz RK, Alexander NJ, Isahakia M, Hamilton MS. Monoclonal antibody to a human germ cell membrane glycoprotein that inhibits fertilization. Science 1984; 225: 342-4.  Back to cited text no. 50
    
51.
Naz RK, Sacco AG, Yurewicz EC. Human spermatozoal FA-1 binds with ZP3 of porcine zona pellucida. J Reprod Immunol 1991; 20: 43-58.  Back to cited text no. 51
    
52.
White D, Weerachatyanukul W, Gadella B, Kamolvarin N, Attar M, et al. Role of sperm sulfogalactosylglycerolipid in mouse sperm-zona pellucida binding. Biol Reprod 2000; 63: 147-55.  Back to cited text no. 52
    
53.
Weerachatyanukul W, Rattanachaiyanont M, Carmona E, Furimsky A, Mai A, et al. Sulfogalactosylglycerolipid is involved in human gamete interaction. Mol Reprod Dev 2001; 60: 569-78.  Back to cited text no. 53
    
54.
De los Reyes M, Barros C. Immunolocalization of proacrosin/acrosin in bovine sperm and sperm penetration through the zona pellucida. Anim Reprod Sci 2000; 58: 215-28.  Back to cited text no. 54
    
55.
Barros C, Capote C, Perez C, Crosby JA, Becker MI, et al. Immunodetection of acrosin during the acrosome reaction of hamster, guinea-pig and human spermatozoa. Biol Res 1992; 25: 31-40.  Back to cited text no. 55
    
56.
NagDas SK, Winfrey VP, Olson GE. Proacrosin-acrosomal matrix binding interactions in ejaculated bovine spermatozoa. Biol Reprod 1996; 54: 111-21.  Back to cited text no. 56
    
57.
Olson GE, Winfrey VP, Bi M, Hardy DM, NagDas SK. Zonadhesin assembly into the hamster sperm acrosomal matrix occurs by distinct targeting strategies during spermiogenesis and maturation in the epididymis. Biol Reprod 2004; 71: 1128-34.  Back to cited text no. 57
    
58.
Foster JA, Herr JC. Interactions of human sperm acrosomal protein SP-10 with the acrosomal membranes. Biol Reprod 1992; 46: 981-90.  Back to cited text no. 58
    
59.
Foster JA, Klotz KL, Flickinger CJ, Thomas TS, Wright RM, et al. Human SP-10: acrosomal distribution, processing, and fate after the acrosome reaction. Biol Reprod 1994; 51: 1222-31.  Back to cited text no. 59
    
60.
Kim KS, Cha MC, Gerton GL. Mouse sperm protein sp56 is a component of the acrosomal matrix. Biol Reprod 2001; 64: 36-43.  Back to cited text no. 60
    
61.
Foster JA, Friday BB, Maulit MT, Blobel C, Winfrey VP, et al. AM67, a secretory component of the guinea pig sperm acrosomal matrix, is related to mouse sperm protein sp56 and the complement component 4-binding proteins. J Biol Chem 1997; 272: 12714-22.  Back to cited text no. 61
    
62.
Ikawa M, Inoue N, Benham AM, Okabe M. Fertilization: a sperm's journey to and interaction with the oocyte. J Clin Invest 2010; 120: 984-94.  Back to cited text no. 62
    
63.
Lu Q, Hasty P, Shur BD. Targeted mutation in beta1,4-galactosyltransferase leads to pituitary insufficiency and neonatal lethality. Dev Biol 1997; 181: 257-67.  Back to cited text no. 63
    
64.
Muro Y, Buffone MG, Okabe M, Gerton GL. Function of the acrosomal matrix: zona pellucida 3 receptor (ZP3R/sp56) is not essential for mouse fertilization. Biol Reprod 2012; 86: 1-6.  Back to cited text no. 64
    
65.
Tardif S, Wilson MD, Wagner R, Hunt P, Gertsenstein M, et al. Zonadhesin is essential for species specificity of sperm adhesion to the egg zona pellucida. J Biol Chem 2010; 285: 24863-70.  Back to cited text no. 65
    
66.
Baba T, Azuma S, Kashiwabara S, Toyoda Y. Sperm from mice carrying a targeted mutation of the acrosin gene can penetrate the oocyte zona pellucida and effect fertilization. J Biol Chem 1994; 269: 31845-9.  Back to cited text no. 66
    
67.
Baba D, Kashiwabara S, Honda A, Yamagata K, Wu Q, et al. Mouse sperm lacking cell surface hyaluronidase PH-20 can pass through the layer of cumulus cells and fertilize the egg. J Biol Chem 2002; 277: 30310-4.  Back to cited text no. 67
    
68.
Hess B, Saftig P, Hartmann D, Coenen R, Lüllmann-Rauch R, et al. Phenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophy. Proc Natl Acad Sci U S A 1996; 93: 14821-6.  Back to cited text no. 68
    
69.
Xu H, Kongmanas K, Kadunganattil S, Smith CE, Rupar T, et al. Arylsulfatase A deficiency causes seminolipid accumulation and a lysosomal storage disorder in Sertoli cells. J Lipid Res 2011; 52: 2187-97.  Back to cited text no. 69
    
70.
Yamashita M, Honda A, Ogura A, Kashiwabara S, Fukami K, et al. Reduced fertility of mouse epididymal sperm lacking Prss21/Tesp5 is rescued by sperm exposure to uterine microenvironment. Genes Cells 2008; 13: 1001-13.  Back to cited text no. 70
    
71.
Yamaguchi R, Muro Y, Isotani A, Tokuhiro K, Takumi K, et al. Disruption of ADAM3 impairs the migration of sperm into oviduct in mouse. Biol Reprod 2009; 81: 142-6.  Back to cited text no. 71
    
72.
Nishimura H, Cho C, Branciforte DR, Myles DG, Primakoff P. Analysis of loss of adhesive function in sperm lacking cyritestin or fertilin. Dev Biol 2001; 233: 204-13.  Back to cited text no. 72
    
73.
Tanphaichitr N, Carmona E, Bou Khalil M, Xu H, Berger T, et al. New insights into sperm-zona pellucida interaction: involvement of sperm lipid rafts. Front Biosci 2007; 12: 1748-66.  Back to cited text no. 73
    
74.
Lyng R, Shur BD. Sperm-egg binding requires a multiplicity of receptor-ligand interactions: new insights into the nature of gamete receptors derived from reproductive tract secretions. Soc Reprod Fertil Suppl 2007; 65: 335-51.  Back to cited text no. 74
    
75.
Redgrove KA, Aitken RJ, Nixon B. More than a simple lock and key mechanism: unraveling the intricacies of sperm-zona pellucida binding. In: Abdelmohsen K, editor. Binding Protein. Rijeka: InTech; 2012. p. 73-122.  Back to cited text no. 75
    
76.
Rajendran L, Simons K. Lipid rafts and membrane dynamics. J Cell Sci 2005; 118: 1099-102.  Back to cited text no. 76
    
77.
Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest 2002; 110: 597-603.  Back to cited text no. 77
    
78.
Tanphaichitr N, Faull KF, Yaghoubian A, Xu H. Lipid rafts and sulfogalactosylglycerolipid (SGG) in sperm functions: consensus and controversy. Trends Glycosci Glycotechnol 2007; 19: 67-83.  Back to cited text no. 78
    
79.
Brown DA, London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem 2000; 275: 17221-4.  Back to cited text no. 79
    
80.
Ohta K, Sato C, Matsuda T, Toriyama M, Lennarz WJ, et al. Isolation and characterization of low density detergent-insoluble membrane (LD-DIM) fraction from sea urchin sperm. Biochem Biophys Res Commun 1999; 258: 616-23.  Back to cited text no. 80
    
81.
Bou Khalil M, Chakrabandhu K, Xu H, Weerachatyanukul W, Buhr M, et al. Sperm capacitation induces an increase in lipid rafts having zona pellucida binding ability and containing sulfogalactosylglycerolipid. Dev Biol 2006; 290: 220-35.  Back to cited text no. 81
    
82.
Nixon B, Bielanowicz A, McLaughlin EA, Tanphaichitr N, Ensslin MA, et al. Composition and significance of detergent resistant membranes in mouse spermatozoa. J Cell Physiol 2009; 218: 122-34.  Back to cited text no. 82
    
83.
van Gestel RA, Brewis IA, Ashton PR, Helms JB, Brouwers JF, et al. Capacitation-dependent concentration of lipid rafts in the apical ridge head area of porcine sperm cells. Mol Hum Reprod 2005; 11: 583-90.  Back to cited text no. 83
    
84.
Sleight SB, Miranda PV, Plaskett NW, Maier B, Lysiak J, et al. Isolation and proteomic analysis of mouse sperm detergent-resistant membrane fractions: evidence for dissociation of lipid rafts during capacitation. Biol Reprod 2005; 73: 721-9.  Back to cited text no. 84
    
85.
Dun MD, Smith ND, Baker MA, Lin M, Aitken RJ, et al. The chaperonin containing TCP1 complex (CCT/TRiC) is involved in mediating sperm-oocyte interaction. J Biol Chem 2011; 286: 36875-87.  Back to cited text no. 85
    
86.
Redgrove KA, Anderson AL, Dun MD, McLaughlin EA, O'Bryan MK, et al. Involvement of multimeric protein complexes in mediating the capacitation-dependent binding of human spermatozoa to homologous zonae pellucidae. Dev Biol 2011; 356: 460-74.  Back to cited text no. 86
    
87.
Redgrove KA, Nixon B, Baker MA, Hetherington L, Baker G, et al. The molecular chaperone HSPA2 plays a key role in regulating the expression of sperm surface receptors that mediate sperm-egg recognition. PLoS One 2012; 7: e50851.  Back to cited text no. 87
    
88.
Pike LJ. The challenge of lipid rafts. J Lipid Res 2009; 50 Suppl: S323-8.  Back to cited text no. 88
    
89.
Huang C, Hepler JR, Chen LT, Gilman AG, Anderson RG, et al. Organization of G proteins and adenylyl cyclase at the plasma membrane. Mol Biol Cell 1997; 8: 2365-78.  Back to cited text no. 89
    
90.
Peterson R, Russell L, Bundman D, Freund M. Evaluation of the purity of boar sperm plasma membranes prepared by nitrogen cavitation. Biol Reprod 1980; 23: 637-45.  Back to cited text no. 90
    
91.
Flesch FM, Voorhout WF, Colenbrander B, van Golde LM, Gadella BM. Use of lectins to characterize plasma membrane preparations from boar spermatozoa: a novel technique for monitoring membrane purity and quantity. Biol Reprod 1998; 59: 1530-9.  Back to cited text no. 91
    
92.
Yurewicz EC, Pack BA, Armant DR, Sacco AG. Porcine zona pellucida ZP3 alpha glycoprotein mediates binding of the biotin-labeled M (r) 55,000 family (ZP3) to boar sperm membrane vesicles. Mol Reprod Dev 1993; 36: 382-9.  Back to cited text no. 92
    
93.
Kongmanas K, Kruevaisayawan H, Saewu A, Sugeng C, Fernandes J, et al. Proteomic characterization of pig sperm anterior head plasma membrane reveals roles of acrosomal proteins in ZP3 binding. J Cell Physiol 2014 Jul 30. doi: 10.1002/jcp.24728. [Epub ahead of print].  Back to cited text no. 93
    
94.
Tsai PS, Garcia-Gil N, van Haeften T, Gadella BM. How pig sperm prepares to fertilize: stable acrosome docking to the plasma membrane. PLoS One 2010; 5: e11204.  Back to cited text no. 94
    
95.
Rosenberg JB, Haberichter SL, Jozwiak MA, Vokac EA, Kroner PA, et al. The role of the D1 domain of the von Willebrand factor propeptide in multimerization of VWF. Blood 2002; 100: 1699-706.  Back to cited text no. 95
    
96.
Baldi E, Casano R, Falsetti C, Krausz C, Maggi M, et al. Intracellular calcium accumulation and responsiveness to progesterone in capacitating human spermatozoa. J Androl 1991; 12: 323-30.  Back to cited text no. 96
    
97.
Vredenburgh-Wilberg WL, Parrish JJ. Intracellular pH of bovine sperm increases during capacitation. Mol Reprod Dev 1995; 40: 490-502.  Back to cited text no. 97
    
98.
Herlyn H, Zischler H. The molecular evolution of sperm zonadhesin. Int J Dev Biol 2008; 52: 781-90.  Back to cited text no. 98
    


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