TCP-11, the product of a mouset-complex gene, plays a role in stimulation of capacitation and inhibition of the spontaneous acrosome reaction

Abstract

Tcp‐11 is a candidate for a distorter gene within the t‐complex on mouse chromosome 17; although t‐complex genes appear to affect sperm function, relatively little is known about mechanisms whereby these genes might play a specific physiological role. We present evidence that the protein TCP‐11 is found on the surface of mature epididymal spermatozoa. Although detected on both the acrosomal cap region of the head and the flagellum of acrosome‐intact cells, it is absent from the heads of acrosome‐reacted cells. When epididymal spermatozoa were incubated in the presence of anti‐TCP‐11 IgG Fab fragments for a total of 120 min and assessed using chlortetracycline fluorescence, we observed a stimulation of capacitation and an inhibition of spontaneous acrosome loss, suggestive of enhanced fertility compared with untreated suspensions. In vitro fertilization experiments confirmed that Fab‐treated suspensions became fertile more quickly and then maintained high fertility. Because these responses were remarkably similar to those obtained using the TRH‐related peptide FPP (fertilization promoting peptide; pGlu‐Glu‐ProNH2) and adenosine, we investigated responses to Fab fragments, FPP, and adenosine. Results indicated that the Fab fragments appear to work at the same extracellular site as FPP, one that is distinct from the adenosine site of action. Further evidence for this conclusion was obtained using pGlu‐Gln‐ProNH2, an FPP‐related tripeptide known to competitively inhibit responses to FPP; as with FPP, pGlu‐Gln‐ProNH2 inhibited the stimulatory effect of Fab fragments in a concentration‐dependent manner. From these results we suggest that TCP‐11 may be the receptor for FPP and that the adenylate clyclase/cyclic AMP pathway may be the signal transduction pathway activated by interactions between extracellular effector molecules (e.g., Fab fragments or FPP acting as an agonist) and TCP‐11. A mechanism such as this that promotes capacitation but inhibits spontaneous acrosome loss in vivo would play a very important role by helping to maximize the fertilizing potential of the few spermatozoa that reach the site of fertilization. The fact that there is a human homolog of Tcp‐11 suggests that this gene could play an important role in regulation of human, as well as mouse, sperm function. Mol. Reprod. Dev. 48:375–382, 1997. © 1997 Wiley‐Liss, Inc.

Role of fertilization promoting peptide FPP in modulating mammalian sperm function

“…When sperm suspensions were incubated in the presence of anti-TCP11 Fab fragments and sampled at 30 and 120 minutes, CTC analysis indicated that capacitation was stimulated significantly during the initial incubation and then spontaneous acrosome reactions were inhibited significantly as incubation continued. In vitro fertilization experiments confirmed that Fab-treated suspensions became fertilizing more quickly than untreated control suspensions and then maintained high fertilizing ability despite the Fab fragments' inhibition of spontaneous acrosome loss (31). The similarity of these responses to those obtained with FPP and adenosine led to further investigations using FPP, adenosine and Fab fragments in various combinations.…”

A novel germ cell protein, SPIF (sperm PKA interacting factor), is essential for the formation of a PKA/TCP11 complex that undergoes conformational and phosphorylation changes upon capacitation

“…Most alleles demonstrating TRD contain lethal mutations that either affect embryonic development (36) or result in male sterility (37). On screening the literature for other genes displaying nonmendelian inheritance, we identified one such gene, Tcp11 , a candidate distorter gene, known to be localized in the acrosome and tail regions of acrosome intact spermatozoa (38). This pattern of protein expression is identical to SPIF, and TCP11 was therefore selected for further examination.…”

“…TCP11 is reported to play an integral role in sperm capacitation and is hypothesized to be the receptor for the putative fertilization‐promoting peptide signaling through the adenylyl cyclase/cAMP pathway (38, 41). As both SPIF and TCP11 have strong links to PKA and all 3 proteins colocalize to the tail regions of spermatozoa (Fig.…”

Effects of a male meiotic driver on male and female transcriptomes in the house mouse

“…In testis, many t haplotype loci previously investigated in the search for genes directly involved in drive showed expression differences in this study. Nearly half of all t haplotype genes that showed DEU are known to be associated with differences between +/t and +/+: Tagap [14], Rps6ka2 [17], Tcte2 [71], Tcte3 [72], Tcp1 [73], Tcp10a and Tcp10b [74,75], Tcp11 [76], Dynlt1c and Dynlt1f [77], Vps52 [78], Fgfr1op [17], Ppp1r11 [79], Synj2 [80] and Tulp4 [81]. Nineteen genes showing alternative transcripts are left which have as yet no known function in the t haplotype, but are now new candidates: the protein kinase Map3k4, sperm genes Ift140, Hmga1, Slc26a8, as well as a mixed collection: Tmem181, Ube2i, Rsph3b, 1700010I14Rik, Rab11b, Rab11fip3, Fkbpl, Afdn, Znrd1as, Gm3448, Tbp, Rps2 and H2-D1.…”