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

Yamazaki, Daisuke; Miyata, Haruhiko; Funato, Yosuke; Fujihara, Yoshitaka; Ikawa, Masahito; Miki, Hiroaki

doi:https://doi.org/10.1242/jcs.182220

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

Yamazaki, Daisuke; Miyata, Haruhiko; Funato, Yosuke et al.

Journal of Cell Science, 2016, 129(9), 1940-1949

Number of Access:707（2025-08-22 01:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78588

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Title	The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and is essential for reproduction
Creator	NRID 1000050422415 1000050422415 CreatorName Yamazaki, Daisuke
	NRID 1000050604732 1000050604732 researchmap permalink hmiyata hmiyata Scopus Author ID 37161837000 37161837000 ORCID 0000-0003-4758-5803 0000-0003-4758-5803 CreatorName Miyata, Haruhiko
	NRID 1000060505775 1000060505775 researchmap permalink read0156495 read0156495 Scopus Author ID 22941032600 22941032600 CreatorName Funato, Yosuke
	NRID 1000070578848 1000070578848 CreatorName Fujihara, Yoshitaka
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	NRID 1000080302602 1000080302602 CreatorName Miki, Hiroaki
Subject	Calcium
	CNNM4
	Hyperactivation
	Sperm capacitation
Abstract	Ca2+ influx triggers sperm capacitation; however, the underlying regulatory mechanisms remain incompletely understood. Here, we show that CNNM4, a Mg2+ transporter, is required for Ca2+ 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 Ca2+ influx during sperm capacitation. Ca2+ imaging analyses demonstrate that Ca2+ influx is perturbed in Cnnm4-deficient sperm, and forced Ca2+ entry into these sperm normalizes the level of tyrosine phosphorylation. Furthermore, we confirm the importance of CNNM4 in sperm by generating germcell- specific Cnnm4-deficient mice. These results suggest a new role of CNNM4 in sperm Ca2+ homeostasis.
Publisher	Company of Biologists Ltd
Source Title	Journal of Cell Science
Volume (Issue)	129(9)
Page	1940-1949
Date of Issued	2016-05
Language	English
Handle URL	https://hdl.handle.net/11094/78588
PISSN	00219533
eISSN	14779137
NCID	AA11720335
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1242/jcs.182220
Relation.isIdenticalTo	PMID 27006114
Access Rights	open access
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Journal of Cell Science. 2016, 129(9), p. 1940-1949
DC.title	The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and is essential for reproduction
DC.creator	Yamazaki, Daisuke
	Miyata, Haruhiko
	Funato, Yosuke
	Fujihara, Yoshitaka
	Ikawa, Masahito
	Miki, Hiroaki
DC.publisher	Company of Biologists Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2016-05
DC.identifier	https://doi.org/10.1242/jcs.182220
DC.subject	Calcium
	CNNM4
	Hyperactivation
	Sperm capacitation
DCTERMS.abstract	Ca2+ influx triggers sperm capacitation; however, the underlying regulatory mechanisms remain incompletely understood. Here, we show that CNNM4, a Mg2+ transporter, is required for Ca2+ 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 Ca2+ influx during sperm capacitation. Ca2+ imaging analyses demonstrate that Ca2+ influx is perturbed in Cnnm4-deficient sperm, and forced Ca2+ entry into these sperm normalizes the level of tyrosine phosphorylation. Furthermore, we confirm the importance of CNNM4 in sperm by generating germcell- specific Cnnm4-deficient mice. These results suggest a new role of CNNM4 in sperm Ca2+ homeostasis.
DC.format	78588
citation_title	The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and is essential for reproduction
citation_author	Yamazaki, Daisuke
	Miyata, Haruhiko
	Funato, Yosuke
	Fujihara, Yoshitaka
	Ikawa, Masahito
	Miki, Hiroaki
citation_publisher	Company of Biologists Ltd
citation_language	English
citation_date	2016-05
citation_journal_title	Journal of Cell Science
citation_volume	129
citation_issue	9
citation_firstpage	1940
citation_lastpage	1949
citation_doi	https://doi.org/10.1242/jcs.182220
citation_pmid	27006114
citation_public_url	https://hdl.handle.net/11094/78588

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

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