The function of chaperone proteins in the assemblage of protein complexes involved in gamete adhesion and fusion processes

Abstract

The remarkable complexity of the molecular events governing adhesion and fusion of the male and female gametes is becoming apparent. Novel research suggests that these highly specific cellular interactions are facilitated by multiprotein complexes that are delivered to and/or assembled on the surface of the gametes by molecular chaperones in preparation for sperm-egg interaction. While the activation of these molecular chaperones and the mechanisms by which they shuttle proteins to the surface of the cell remain the subject of ongoing investigation, a compelling suggestion is that these processes are augmented by dynamic membrane microdomains or lipid rafts that migrate to the apical region of the sperm head after capacitation. Preliminary studies of the oocyte plasma membrane have also revealed the presence of lipid rafts comprising several molecular chaperones, raising the possibility that similar mechanisms may be involved in the activation of maternal fusion machinery and the regulation of oocyte plasma membrane integrity. Despite these findings, the analysis of oocyte surface multiprotein complexes is currently lacking. Further analyses of the intermediary proteins that facilitate the expression of key players in sperm-egg fusion are likely to deliver important insights into this unique event, which culminates in the cytoplasmic continuity of the male and female gametes.Reproduction (2013) 145 R31-R42

Proteomic markers of low and high fertility bovine spermatozoa separated by Percoll gradient

“…All involve the same proteins, namely molecular chaperones HSPA2 and HSPAA1, as well as Subunits 1 and 5 of the chaperonin‐containing‐TCP1 complex. Indeed, evidence suggests that these chaperones and chaperonins are implicated in the assembly of zona pellucida recognition protein complex, and the translocation of these complexes to the sperm surface during capacitation (Bromfield & Nixon, ). In humans, impaired sperm–zona binding is associated with reduced expression of HSPA2 from the sperm proteome (Redgrove et al, ).…”

Free cholesterol and cholesterol esters in bovine oocytes: Implications in survival and membrane raft organization after cryopreservation

“…Conversely, a sub-physiological level of cholesterol in mouse oocytes causes a delay in second polar body extrusion and low fertilization rates [18]. Cholesterol mediates membrane curvature during fusion events [19] and recent advances start to reveal common mechanisms also in gamete interaction [18,20,21]. It is clear that abnormal levels of membrane cholesterol could adversely affect fertilization and subsequent embryo development.…”

Paternal exposure to testis cancer chemotherapeutics alters sperm fertilizing capacity and affects gene expression in the eight-cell stage rat embryo

“…Furthermore, protein disulphide isomerase family A, member 3 (PDIA3) was also upregulated in epididymal spermatozoa following 9 weeks of treatment with BEP (Maselli et al, 2012). As recent data have suggested an important role for these upregulated proteins in fertilization (Ellerman et al, 2006;Bromfield & Nixon, 2013), we did Western blot analysis as an independent confirmation of these findings (Fig. 1).…”

“…Various HSP family members are the subject of dynamic redistribution as spermatozoa undergo capacitation, with current models suggesting that the phosphorylation of these chaperones during capacitation triggers their active role in the assembly of zona pellucida recognition proteins into complexes and/or the translocation of these complexes to the surface of spermatozoa in preparation for fertilization (Ecroyd et al, 2003;Asquith et al, 2004;Nixon et al, 2005;Gadella, 2008). Thus, with their major involvement in the regulation of zona pellucida binding, it is expected that chaperone-laden complexes may also assist in the activation of the fusion machinery and/or organization of functional fusion complexes (Bromfield & Nixon, 2013). Among the other chaperones present on the sperm surface that mediate zona pellucida interactions are CCT/TriC (Dun et al, 2011), HSPA2 (Naaby-Hansen & Herr, 2010Redgrove et al, 2012Redgrove et al, , 2013, HSPD1 (Boilard et al, 2004;Asquith et al, 2005), HSPA5 (Boilard et al, 2004) and HSPE1 (Walsh et al, 2008).…”