Human t-Complex Protein 11 (TCP11), a Testis-Specific Gene Product, Is a Potential Determinant of the Sperm Morphology

Abstract

Fertilization promoting peptid (FPP) is essential for capacitation and acrosome reaction. The mouse t-complex protein 11 (Tcp11) gene, which encodes the receptor of FPP, plays an important role in fertilization. We had identified three alternative splicing products of its human homologous gene, TCP11, nominated as TCP11a, TCP11b and TCP11c. Their testis-specific expression had been noted, suggesting that TCP11 may play an important role in spermatogenesis and sperm function. In order to explore the function of TCP11, we investigated its expression, subcellular location and binding protein in the sperm. RT-PCR assay shows that all isoforms of TCP11 are present in both human testis and sperm. However, we could only detect the expression of 56-kDa protein, representing TCP11a and TCP11c, but not TCP11b, by western blot analysis. Furthermore, the expression level of 56-kDa TCP11 protein was lower by about threefold in sperm samples containing over 15% of coiled sperms than the level in sperm samples with normal morphology. The coiled sperm, which shows a coiling or bending back of the tail on itself, is associated with infertility. In addition, several TCP11a-binding proteins were isolated using full-length TCP11a as bait. Among them, we focused on outer dense fiber 1 (ODF1), a component of sperm tail outer dense fibers, because outer dense fibers contribute to the distinct morphology and the function of sperm tail. Co-immunoprecipitation assays of sperm cell extracts confirmed that TCP11 protein interacted with ODF1. These results suggest that TCP11 may be responsible for the sperm tail morphology and motility.

Major protein alterations in spermatozoa from infertile men with unilateral varicocele

“… [ 81 ] Q8WWU5 TCP11 T-complex protein 11 homolog isoform 1 Fertile group only May play an important role in sperm function and fertility. [ 82 , 83 ] Q8WYR4 RSPH1 Radial spoke head 1 homolog ↓ May play an important role in male meiosis. [ 84 , 85 ] Q96A08 HIST1H2BA Histone H2B type 1-A ↑ Variant histone specifically required to direct the transformation of dissociating nucleosomes to protamine in male germ cells.…”

“…May help to maintain the passive elastic structures and elastic recoil of the sperm tail. [ 73 , 83 , 87 ] Q96QH8 SPACA5 Sperm acrosome-associated protein 5 precursor Fertile group only Sperm acrosome-associated protein 5. [ 88 ] Q99497 PARK7 Protein DJ-1 ↑ It acts as atypical peroxiredoxin –like peroxidase that scavenges hydrogen peroxide.…”

Sperm morphology: assessment, pathophysiology, clinical relevance, and state of the art in 2017

“…The level of expression of TCP11 (human y‐complex protein 11) is 70% less in samples containing high rates of spermatozoa with coiled tails (Liu et al ., ). Their results show that TCP11 interacts with ODF1 (a major component of outer dense fibers) that plays a role in flagellar morphogenesis.…”

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

“…The human genome also encodes homologs of the other identified SPIF complex proteins: TCP11 and PRKACA2. It has been demonstrated that Tcp11 is not expressed in the testes of some patients with azoospermia (49), and expression is reduced in the sperm of males with poor morphology (50). It will be interesting to extend this study into human samples and assess the role of the SPIF/TCP11/PKAC complex in human capacitation and fertility.…”