The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and is essential for reproduction.

نویسندگان

  • Daisuke Yamazaki
  • Haruhiko Miyata
  • Yosuke Funato
  • Yoshitaka Fujihara
  • Masahito Ikawa
  • Hiroaki Miki
چکیده

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.

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Rebuttal from Francisco J. Arjona and Jeroen H. F. de Baaij

We fully agree with Funato and colleagues on the relevance of CNNM proteins for the maintenance of Mg2+ homeostasis (Funato et al. 2018). Both of our papers summarize the solid body of evidence demonstrating thatCNNM2 is key for renalMg2+ handling, while CNNM4 regulates intestinal Mg2+ transport. Nevertheless, we do not share the conclusions presented by Funato and colleagues suggesting that CN...

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عنوان ژورنال:
  • Journal of cell science

دوره 129 9  شماره 

صفحات  -

تاریخ انتشار 2016