| First Author | Yang F | Year | 2022 |
| Journal | Development | Volume | 149 |
| Issue | 2 | PubMed ID | 34919125 |
| Mgi Jnum | J:316788 | Mgi Id | MGI:6842326 |
| Doi | 10.1242/dev.199988 | Citation | Yang F, et al. (2021) C2CD6 regulates targeting and organization of the CatSper calcium channel complex in sperm flagella. Development :dev199988 |
| abstractText | The CatSper cation channel is essential for sperm capacitation and male fertility. The multi-subunit CatSper complexes form highly organized calcium signaling nanodomains on flagellar membranes. Here we report identification of an uncharacterized protein C2CD6 as a novel subunit of the CatSper complex. C2CD6 contains a calcium-dependent membrane targeting C2 domain. C2CD6 associates with the CatSper calcium-selective core forming subunits. Deficiency of C2CD6 depletes the CatSper nanodomains from the flagellum and results in male sterility. C2CD6-deficient sperm are defective in hyperactivation and fail to fertilize oocytes both in vitro and in vivo. CatSper currents are present but at a significantly lower level in C2CD6-deficient sperm. Transient treatments with either Ca2+ ionophore, starvation, or a combination of both restore the fertilization capacity of C2CD6-deficient sperm. C2CD6 interacts with EFCAB9, a pH-dependent calcium sensor in the CatSper complex. We postulate that C2CD6 facilitates incorporation of the CatSper complex into the flagellar plasma membrane and may function as a calcium sensor. The identification of C2CD6 may enable the long-sought reconstitution of the CatSper ion channel complex in a heterologous system for male contraceptive development. |
