Human t-complex protein 11 (TCP11), a testis-specific gene product, is a potential determinant of the sperm morphology.

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.