| First Author | Hwang JY | Year | 2019 |
| Journal | Cell | Volume | 177 |
| Issue | 6 | Pages | 1480-1494.e19 |
| PubMed ID | 31056283 | Mgi Jnum | J:276402 |
| Mgi Id | MGI:6316499 | Doi | 10.1016/j.cell.2019.03.047 |
| Citation | Hwang JY, et al. (2019) Dual Sensing of Physiologic pH and Calcium by EFCAB9 Regulates Sperm Motility. Cell 177(6):1480-1494.e19 |
| abstractText | Varying pH of luminal fluid along the female reproductive tract is a physiological cue that modulates sperm motility. CatSper is a sperm-specific, pH-sensitive calcium channel essential for hyperactivated motility and male fertility. Multi-subunit CatSper channel complexes organize linear Ca(2+) signaling nanodomains along the sperm tail. Here, we identify EF-hand calcium-binding domain-containing protein 9 (EFCAB9) as a bifunctional, cytoplasmic machine modulating the channel activity and the domain organization of CatSper. Knockout mice studies demonstrate that EFCAB9, in complex with the CatSper subunit, CATSPERzeta, is essential for pH-dependent and Ca(2+)-sensitive activation of the CatSper channel. In the absence of EFCAB9, sperm motility and fertility is compromised, and the linear arrangement of the Ca(2+) signaling domains is disrupted. EFCAB9 interacts directly with CATSPERzeta in a Ca(2+)-dependent manner and dissociates at elevated pH. These observations suggest that EFCAB9 is a long-sought, intracellular, pH-dependent Ca(2+) sensor that triggers changes in sperm motility. |
