| First Author | Yamazaki D | Year | 2016 |
| Journal | J Cell Sci | Volume | 129 |
| Issue | 9 | Pages | 1940-9 |
| PubMed ID | 27006114 | Mgi Jnum | J:246429 |
| Mgi Id | MGI:5924688 | Doi | 10.1242/jcs.182220 |
| Citation | Yamazaki D, et al. (2016) The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and is essential for reproduction. J Cell Sci 129(9):1940-9 |
| abstractText | Ca(2+) influx triggers sperm capacitation; however, the underlying regulatory mechanisms remain incompletely understood. Here, we show that CNNM4, a Mg(2+) transporter, is required for Ca(2+) influx during capacitation. We find that Cnnm4-deficient male mice are almost infertile because of sperm dysfunction. Motion analyses show that hyperactivation, a qualitative change in the mode of sperm motility during capacitation, is abrogated in Cnnm4-deficient sperm. In contrast, tyrosine phosphorylation of flagellar proteins, a hallmark of capacitation, is excessively augmented. These seemingly paradoxical phenotypes of Cnnm4-deficient sperm are very similar to those of sperm lacking a functional cation channel of sperm (CatSper) channel, which plays an essential role in Ca(2+) influx during sperm capacitation. Ca(2+) imaging analyses demonstrate that Ca(2+) influx is perturbed in Cnnm4-deficient sperm, and forced Ca(2+) entry into these sperm normalizes the level of tyrosine phosphorylation. Furthermore, we confirm the importance of CNNM4 in sperm by generating germ-cell-specific Cnnm4-deficient mice. These results suggest a new role of CNNM4 in sperm Ca(2+) homeostasis. |
