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Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins

Dysfunction of the basement membrane protein QBRICK provokes Fraser syndrome, which results in renal dysmorphogenesis, cryptophthalmos, syndactyly, and dystrophic epidermolysis bullosa through unknown mechanisms. Here, we show that integrin α8β1 binding to basement membranes was significantly impair...

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Detalles Bibliográficos
Autores principales: Kiyozumi, Daiji, Takeichi, Makiko, Nakano, Itsuko, Sato, Yuya, Fukuda, Tomohiko, Sekiguchi, Kiyotoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365501/
https://www.ncbi.nlm.nih.gov/pubmed/22613833
http://dx.doi.org/10.1083/jcb.201203065
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author Kiyozumi, Daiji
Takeichi, Makiko
Nakano, Itsuko
Sato, Yuya
Fukuda, Tomohiko
Sekiguchi, Kiyotoshi
author_facet Kiyozumi, Daiji
Takeichi, Makiko
Nakano, Itsuko
Sato, Yuya
Fukuda, Tomohiko
Sekiguchi, Kiyotoshi
author_sort Kiyozumi, Daiji
collection PubMed
description Dysfunction of the basement membrane protein QBRICK provokes Fraser syndrome, which results in renal dysmorphogenesis, cryptophthalmos, syndactyly, and dystrophic epidermolysis bullosa through unknown mechanisms. Here, we show that integrin α8β1 binding to basement membranes was significantly impaired in Qbrick-null mice. This impaired integrin α8β1 binding was not a direct consequence of the loss of QBRICK, which itself is a ligand of integrin α8β1, because knock-in mice with a mutation in the integrin-binding site of QBRICK developed normally and do not exhibit any defects in integrin α8β1 binding. Instead, the loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1–dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome.
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spelling pubmed-33655012012-11-28 Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins Kiyozumi, Daiji Takeichi, Makiko Nakano, Itsuko Sato, Yuya Fukuda, Tomohiko Sekiguchi, Kiyotoshi J Cell Biol Research Articles Dysfunction of the basement membrane protein QBRICK provokes Fraser syndrome, which results in renal dysmorphogenesis, cryptophthalmos, syndactyly, and dystrophic epidermolysis bullosa through unknown mechanisms. Here, we show that integrin α8β1 binding to basement membranes was significantly impaired in Qbrick-null mice. This impaired integrin α8β1 binding was not a direct consequence of the loss of QBRICK, which itself is a ligand of integrin α8β1, because knock-in mice with a mutation in the integrin-binding site of QBRICK developed normally and do not exhibit any defects in integrin α8β1 binding. Instead, the loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1–dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome. The Rockefeller University Press 2012-05-28 /pmc/articles/PMC3365501/ /pubmed/22613833 http://dx.doi.org/10.1083/jcb.201203065 Text en © 2012 Kiyozumi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Kiyozumi, Daiji
Takeichi, Makiko
Nakano, Itsuko
Sato, Yuya
Fukuda, Tomohiko
Sekiguchi, Kiyotoshi
Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins
title Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins
title_full Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins
title_fullStr Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins
title_full_unstemmed Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins
title_short Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins
title_sort basement membrane assembly of the integrin α8β1 ligand nephronectin requires fraser syndrome–associated proteins
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365501/
https://www.ncbi.nlm.nih.gov/pubmed/22613833
http://dx.doi.org/10.1083/jcb.201203065
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