Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility

Wang, Haoting; Shimada, Keisuke; Pham, Anh Hoang; Oyama, Yuki; Kamoshita, Maki; Kobayashi, Hiroko; Oura, Seiya; Yabuta, Norikazu; Ikawa, Masahito; Miyata, Haruhiko

doi:https://doi.org/10.1038/S41467-025-63705-7

Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility

Wang, Haoting; Shimada, Keisuke; Pham, Anh Hoang et al.

Nature Communications, 2025, 16, 8238

Number of Access:102（2026-02-05 22:24 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/103487

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Title	Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility
Creator	CreatorName Wang, Haoting
	NRID 1000060779601 1000060779601 ORCID 0000-0003-3739-7163 0000-0003-3739-7163 researchmap permalink nununununu nununununu Scopus Author ID 56479808000 56479808000 CreatorName Shimada, Keisuke
	CreatorName Pham, Anh Hoang
	CreatorName Oyama, Yuki
	NRID 1000070930288 1000070930288 CreatorName Kamoshita, Maki
	ORCID 0000-0003-3348-733X 0000-0003-3348-733X researchmap permalink 2kuro11 2kuro11 Scopus Author ID 59308696900 59308696900 CreatorName Kobayashi, Hiroko
	ORCID 0000-0002-7606-732X 0000-0002-7606-732X researchmap permalink seiyao seiyao Scopus Author ID 57204003196 57204003196 CreatorName Oura, Seiya
	NRID 1000010343245 1000010343245 ORCID 0000-0001-6911-8582 0000-0001-6911-8582 researchmap permalink read0092303 read0092303 Scopus Author ID 6603956412 6603956412 CreatorName Yabuta, Norikazu
	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 1000050604732 1000050604732 ORCID 0000-0003-4758-5803 0000-0003-4758-5803 researchmap permalink hmiyata hmiyata Scopus Author ID 37161837000 37161837000 CreatorName Miyata, Haruhiko
Description	Wang H., Shimada K., Pham A.H., et al. Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility. Nature Communications 16, 8238 (2025); https://doi.org/10.1038/S41467-025-63705-7.
Abstract	Radial spokes (RSs) are conserved multimolecular structures attached to the axonemal microtubule doublets and are essential for the motility control of both cilia and sperm flagella. CFAP91, an RS3 protein, is implicated in human male infertility, yet its molecular function remains poorly understood. Here, we demonstrate that Cfap91 knockout (KO) mice exhibit impaired sperm flagellum formation and male infertility. Using a transgenic rescue model expressing FLAG- and BioID2-tagged CFAP91, we reveal that CFAP91 immunoprecipitates with RS3 proteins CFAP251 and LRRC23, whose localization is disrupted in Cfap91 KO sperm flagella. In addition, proximity labeling in mature spermatozoa identifies EFCAB5 as a sperm-specific CFAP91-proximal component. We show that Efcab5 KO males exhibit reduced sperm motility and fertility. Our findings establish CFAP91 as an essential scaffolder of RS3 assembly and EFCAB5 as a sperm-specialized movement regulator, advancing understanding of axonemal specialization in mammalian spermatozoa and its relevance to male infertility.
Publisher	Nature Research
Source Title	Nature Communications
Volume (Issue)	16
Page	8238
Date of Issued	2025-09-10
Language	English
Handle URL	https://hdl.handle.net/11094/103487
eISSN	20411723
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/S41467-025-63705-7
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Nature Communications. 2025, 16, p. 8238
DC.title	Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility
DC.creator	Wang, Haoting
	Shimada, Keisuke
	Pham, Anh Hoang
	Oyama, Yuki
	Kamoshita, Maki
	Kobayashi, Hiroko
	Oura, Seiya
	Yabuta, Norikazu
	Ikawa, Masahito
	Miyata, Haruhiko
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-09-10
DC.identifier	https://doi.org/10.1038/S41467-025-63705-7
DC.description	Wang H., Shimada K., Pham A.H., et al. Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility. Nature Communications 16, 8238 (2025); https://doi.org/10.1038/S41467-025-63705-7.
DCTERMS.abstract	Radial spokes (RSs) are conserved multimolecular structures attached to the axonemal microtubule doublets and are essential for the motility control of both cilia and sperm flagella. CFAP91, an RS3 protein, is implicated in human male infertility, yet its molecular function remains poorly understood. Here, we demonstrate that Cfap91 knockout (KO) mice exhibit impaired sperm flagellum formation and male infertility. Using a transgenic rescue model expressing FLAG- and BioID2-tagged CFAP91, we reveal that CFAP91 immunoprecipitates with RS3 proteins CFAP251 and LRRC23, whose localization is disrupted in Cfap91 KO sperm flagella. In addition, proximity labeling in mature spermatozoa identifies EFCAB5 as a sperm-specific CFAP91-proximal component. We show that Efcab5 KO males exhibit reduced sperm motility and fertility. Our findings establish CFAP91 as an essential scaffolder of RS3 assembly and EFCAB5 as a sperm-specialized movement regulator, advancing understanding of axonemal specialization in mammalian spermatozoa and its relevance to male infertility.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	103487
citation_title	Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility
citation_author	Wang, Haoting
	Shimada, Keisuke
	Pham, Anh Hoang
	Oyama, Yuki
	Kamoshita, Maki
	Kobayashi, Hiroko
	Oura, Seiya
	Yabuta, Norikazu
	Ikawa, Masahito
	Miyata, Haruhiko
citation_publisher	Nature Research
citation_language	English
citation_date	2025-09-10
citation_journal_title	Nature Communications
citation_volume	16
citation_firstpage	8238
citation_doi	https://doi.org/10.1038/S41467-025-63705-7
citation_public_url	https://hdl.handle.net/11094/103487

Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility

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