Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion

Inoue, Naokazu; Hamada, Daizo; Kamikubo, Hironari; Hirata, Kunio; Kataoka, Mikio; Yamamoto, Masaki; Ikawa, Masahito; Okabe, Masaru; Hagihara, Yoshihisa

doi:https://doi.org/10.1242/dev.094854

Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion

Inoue, Naokazu; Hamada, Daizo; Kamikubo, Hironari et al.

Development, 2013, 140(15), 3221-3229

アクセス数:220件（2025-04-18 02:30 集計）

固定URL: https://hdl.handle.net/11094/78606

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タイトル	Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion
著者	NRID 1000050379096 1000050379096 著者名 Inoue, Naokazu
	NRID 1000060372132 1000060372132 著者名 Hamada, Daizo
	NRID 1000020311128 1000020311128 著者名 Kamikubo, Hironari
	NRID 1000020373524 1000020373524 著者名 Hirata, Kunio
	NRID 1000030150254 1000030150254 著者名 Kataoka, Mikio
	NRID 1000060241254 1000060241254 著者名 Yamamoto, Masaki
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 著者名 Ikawa, Masahito
	NRID 1000030089875 1000030089875 著者名 Okabe, Masaru
	NRID 1000050357761 1000050357761 著者名 Hagihara, Yoshihisa
キーワード等	IZUMO1
	Membrane fusion
	Sperm-egg fusion
抄録	Although the membrane fusion of spermatozoon and egg cells is the central event of fertilization, the underlying molecular mechanism remains virtually unknown. Gene disruption studies have showed that IZUMO1 on spermatozoon and CD9 on oocyte are essential transmembrane proteins in sperm-egg fusion. In this study, we dissected IZUMO1 protein to determine the domains that were required for the function of sperm-egg fusion. We found that a fragment of the N terminus (Asp5 to Leu113) interacts with fertilization inhibitory antibodies. It also binds to the egg surface and effectively inhibits fusion in vitro. We named this fragment 'IZUMO1 putative functional fragment (IZUMO1PFF)'. Surprisingly, IZUMO1PFF still maintains binding ability on the egg surface of Cd9-/- eggs. A series of biophysical measurements using circular dichroism, sedimentation equilibrium and small angle X-ray scattering revealed that IZUMO1PFF is composed of an N-terminal unfolded structure and a C-terminal ellipsoidal helix dimer. Egg binding and fusion inhibition were not observed in the IZUMO1PFF derivative, which was incapable of helix formation. These findings suggest that the formation of a helical dimer at the N-terminal region of IZUMO1 is required for its function. Cos-7 cells expressing the whole IZUMO1 molecule bound to eggs, and IZUMO1 accumulated at the interface between the two cells, but fusion was not observed. These observations suggest that IZUMO1 alone cannot promote sperm-egg membrane fusion, but it works as a factor that is related to the cellular surface interaction, such as the tethering of the membranes by a helical region corresponding to IZUMO1PFF -core.
出版者	Company of Biologists Ltd
収録物名	Development
巻(号)	140(15)
ページ	3221-3229
刊行年月	2013-08
言語	英語
ハンドルURL	https://hdl.handle.net/11094/78606
PISSN	09501991
eISSN	14779129
NCID	AA10667805
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1242/dev.094854
関連情報 (isIdenticalTo)	PMID 23824580
アクセス権	open access
権利情報	© 2013. Published by The Company of Biologists Ltd.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Development. 2013, 140(15), p. 3221-3229
DC.title	Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion
DC.creator	Inoue, Naokazu
	Hamada, Daizo
	Kamikubo, Hironari
	Hirata, Kunio
	Kataoka, Mikio
	Yamamoto, Masaki
	Ikawa, Masahito
	Okabe, Masaru
	Hagihara, Yoshihisa
DC.publisher	Company of Biologists Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2013-08
DC.identifier	https://doi.org/10.1242/dev.094854
DC.subject	IZUMO1
	Membrane fusion
	Sperm-egg fusion
DCTERMS.abstract	Although the membrane fusion of spermatozoon and egg cells is the central event of fertilization, the underlying molecular mechanism remains virtually unknown. Gene disruption studies have showed that IZUMO1 on spermatozoon and CD9 on oocyte are essential transmembrane proteins in sperm-egg fusion. In this study, we dissected IZUMO1 protein to determine the domains that were required for the function of sperm-egg fusion. We found that a fragment of the N terminus (Asp5 to Leu113) interacts with fertilization inhibitory antibodies. It also binds to the egg surface and effectively inhibits fusion in vitro. We named this fragment 'IZUMO1 putative functional fragment (IZUMO1PFF)'. Surprisingly, IZUMO1PFF still maintains binding ability on the egg surface of Cd9-/- eggs. A series of biophysical measurements using circular dichroism, sedimentation equilibrium and small angle X-ray scattering revealed that IZUMO1PFF is composed of an N-terminal unfolded structure and a C-terminal ellipsoidal helix dimer. Egg binding and fusion inhibition were not observed in the IZUMO1PFF derivative, which was incapable of helix formation. These findings suggest that the formation of a helical dimer at the N-terminal region of IZUMO1 is required for its function. Cos-7 cells expressing the whole IZUMO1 molecule bound to eggs, and IZUMO1 accumulated at the interface between the two cells, but fusion was not observed. These observations suggest that IZUMO1 alone cannot promote sperm-egg membrane fusion, but it works as a factor that is related to the cellular surface interaction, such as the tethering of the membranes by a helical region corresponding to IZUMO1PFF -core.
DC.rights	© 2013. Published by The Company of Biologists Ltd.
DC.format	78606
citation_title	Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion
citation_author	Inoue, Naokazu
	Hamada, Daizo
	Kamikubo, Hironari
	Hirata, Kunio
	Kataoka, Mikio
	Yamamoto, Masaki
	Ikawa, Masahito
	Okabe, Masaru
	Hagihara, Yoshihisa
citation_publisher	Company of Biologists Ltd
citation_language	英語
citation_date	2013-08
citation_journal_title	Development
citation_volume	140
citation_issue	15
citation_firstpage	3221
citation_lastpage	3229
citation_doi	https://doi.org/10.1242/dev.094854
citation_pmid	23824580
citation_public_url	https://hdl.handle.net/11094/78606

Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion

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