Polydom/SVEP1 Is a Ligand for Integrin α9β1

Sato, Ryoko; Nakano, Itsuko; Ozawa, Akio; Sato, Yuya; Takeichi, Makiko; Kiyozumi, Daiji; Yamazaki, Kiyoshi; Yasunaga, Teruo; Futaki, Sugiko; Sekiguchi, Kiyotoshi

doi:https://doi.org/10.1074/jbc.M112.355016

Polydom/SVEP1 Is a Ligand for Integrin α9β1

Sato, Ryoko; Nakano, Itsuko; Ozawa, Akio et al.

Journal of Biological Chemistry, 2012, 287(30), 25615-25630

アクセス数:468件（2025-06-06 08:14 集計）

固定URL: https://hdl.handle.net/11094/71417

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タイトル	Polydom/SVEP1 Is a Ligand for Integrin α9β1
著者	著者名 Sato, Ryoko 著者の別表記 Nishiuchi, Ryoko
	著者名 Nakano, Itsuko
	著者名 Ozawa, Akio
	著者名 Sato, Yuya
	著者名 Takeichi, Makiko
	NRID 1000070452430 1000070452430 ORCID 0000-0003-3289-227X 0000-0003-3289-227X researchmap permalink dkiyozumi dkiyozumi Scopus Author ID 6506341053 6506341053 著者名 Kiyozumi, Daiji
	著者名 Yamazaki, Kiyoshi
	NRID 1000020260630 1000020260630 著者名 Yasunaga, Teruo
	NRID 1000000403014 1000000403014 著者名 Futaki, Sugiko
	NRID 1000050187845 1000050187845 researchmap permalink read0054833 read0054833 Scopus Author ID 7201662709 7201662709 ORCID 0000-0002-6433-1410 0000-0002-6433-1410 著者名 Sekiguchi, Kiyotoshi
内容	This research was originally published in the Journal of Biological Chemistry. Ryoko Sato-Nishiuchi, Itsuko Nakano, Akio Ozawa, Yuya Sato, Makiko Takeichi, Daiji Kiyozumi, Kiyoshi Yamazaki, Teruo Yasunaga, Sugiko Futaki and Kiyotoshi Sekiguchi. Polydom/SVEP1 Is a Ligand for Integrin α9β1. J. Biol. Chem. 2012; 287: 25615-25630 © the American Society for Biochemistry and Molecular Biology
抄録	A variety of proteins, including tenascin-C and osteopontin, have been identified as ligands for integrin α9β1. However, their affinities for integrin α9β1 are apparently much lower than those of other integrins (e.g. α3β1, α5β1, and α8β1) for their specific ligands, leaving the possibility that physiological ligands for integrin α9β1 still remain unidentified. In this study, we found that polydom (also named SVEP1) mediates cell adhesion in an integrin α9β1-dependent manner and binds directly to recombinant integrin α9β1 with an affinity that far exceeds those of the known ligands. Using a series of recombinant polydom proteins with N-terminal deletions, we mapped the integrin-binding site to the 21st complement control protein domain. Alanine-scanning mutagenesis revealed that the EDDMMEVPY sequence (amino acids 2636–2644) in the 21st complement control protein domain was involved in the binding to integrin α9β1 and that Glu2641 was the critical acidic residue for the integrin binding. The importance of this sequence was further confirmed by integrin binding inhibition assays using synthetic peptides. Immunohistochemical analyses of mouse embryonic tissues showed that polydom colocalized with integrin α9 in the stomach, intestine, and other organs. Furthermore, in situ integrin α9β1 binding assays using frozen mouse tissues showed that polydom accounts for most, but not all, of the integrin α9β1 ligands in tissues. Taken together, the present findings indicate that polydom is a hitherto unknown ligand for integrin α9β1 that functions as a physiological ligand in vivo.
出版者	American Society for Biochemistry and Molecular Biology
収録物名	Journal of Biological Chemistry
巻(号)	287(30)
ページ	25615-25630
刊行年月	2012-07
言語	英語
ハンドルURL	https://hdl.handle.net/11094/71417
eISSN	1083351X
NCID	AA1202441X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1074/jbc.M112.355016
アクセス権	open access
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

論文詳細を表示

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
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2012, 287(30), p. 25615-25630
DC.title	Polydom/SVEP1 Is a Ligand for Integrin α9β1
DC.creator	Sato, Ryoko
	Nakano, Itsuko
	Ozawa, Akio
	Sato, Yuya
	Takeichi, Makiko
	Kiyozumi, Daiji
	Yamazaki, Kiyoshi
	Yasunaga, Teruo
	Futaki, Sugiko
	Sekiguchi, Kiyotoshi
DC.creator	Nishiuchi, Ryoko
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2012-07
DC.identifier	https://doi.org/10.1074/jbc.M112.355016
DC.description	This research was originally published in the Journal of Biological Chemistry. Ryoko Sato-Nishiuchi, Itsuko Nakano, Akio Ozawa, Yuya Sato, Makiko Takeichi, Daiji Kiyozumi, Kiyoshi Yamazaki, Teruo Yasunaga, Sugiko Futaki and Kiyotoshi Sekiguchi. Polydom/SVEP1 Is a Ligand for Integrin α9β1. J. Biol. Chem. 2012; 287: 25615-25630 © the American Society for Biochemistry and Molecular Biology
DCTERMS.abstract	A variety of proteins, including tenascin-C and osteopontin, have been identified as ligands for integrin α9β1. However, their affinities for integrin α9β1 are apparently much lower than those of other integrins (e.g. α3β1, α5β1, and α8β1) for their specific ligands, leaving the possibility that physiological ligands for integrin α9β1 still remain unidentified. In this study, we found that polydom (also named SVEP1) mediates cell adhesion in an integrin α9β1-dependent manner and binds directly to recombinant integrin α9β1 with an affinity that far exceeds those of the known ligands. Using a series of recombinant polydom proteins with N-terminal deletions, we mapped the integrin-binding site to the 21st complement control protein domain. Alanine-scanning mutagenesis revealed that the EDDMMEVPY sequence (amino acids 2636–2644) in the 21st complement control protein domain was involved in the binding to integrin α9β1 and that Glu2641 was the critical acidic residue for the integrin binding. The importance of this sequence was further confirmed by integrin binding inhibition assays using synthetic peptides. Immunohistochemical analyses of mouse embryonic tissues showed that polydom colocalized with integrin α9 in the stomach, intestine, and other organs. Furthermore, in situ integrin α9β1 binding assays using frozen mouse tissues showed that polydom accounts for most, but not all, of the integrin α9β1 ligands in tissues. Taken together, the present findings indicate that polydom is a hitherto unknown ligand for integrin α9β1 that functions as a physiological ligand in vivo.
DC.format	71417
citation_title	Polydom/SVEP1 Is a Ligand for Integrin α9β1
citation_author	Sato, Ryoko
	Nakano, Itsuko
	Ozawa, Akio
	Sato, Yuya
	Takeichi, Makiko
	Kiyozumi, Daiji
	Yamazaki, Kiyoshi
	Yasunaga, Teruo
	Futaki, Sugiko
	Sekiguchi, Kiyotoshi
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	英語
citation_date	2012-07
citation_journal_title	Journal of Biological Chemistry
citation_volume	287
citation_issue	30
citation_firstpage	25615
citation_lastpage	25630
citation_doi	https://doi.org/10.1074/jbc.M112.355016
citation_public_url	https://hdl.handle.net/11094/71417