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Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney

The epithelial–mesenchymal interactions required for kidney organogenesis are disrupted in mice lacking the integrin α8β1. None of this integrin's known ligands, however, appears to account for this phenotype. To identify a more relevant ligand, a soluble integrin α8β1 heterodimer fused to alka...

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Autores principales: Brandenberger, Ralph, Schmidt, Andrea, Linton, James, Wang, Denan, Backus, Carey, Denda, Sumiko, Müller, Ullrich, Reichardt, Louis F.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150762/
https://www.ncbi.nlm.nih.gov/pubmed/11470831
http://dx.doi.org/10.1083/jcb.200103069
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author Brandenberger, Ralph
Schmidt, Andrea
Linton, James
Wang, Denan
Backus, Carey
Denda, Sumiko
Müller, Ullrich
Reichardt, Louis F.
author_facet Brandenberger, Ralph
Schmidt, Andrea
Linton, James
Wang, Denan
Backus, Carey
Denda, Sumiko
Müller, Ullrich
Reichardt, Louis F.
author_sort Brandenberger, Ralph
collection PubMed
description The epithelial–mesenchymal interactions required for kidney organogenesis are disrupted in mice lacking the integrin α8β1. None of this integrin's known ligands, however, appears to account for this phenotype. To identify a more relevant ligand, a soluble integrin α8β1 heterodimer fused to alkaline phosphatase (AP) has been used to probe blots and cDNA libraries. In newborn mouse kidney extracts, α8β1-AP detects a novel ligand of 70–90 kD. This protein, named nephronectin, is an extracellular matrix protein with five EGF-like repeats, a mucin region containing a RGD sequence, and a COOH-terminal MAM domain. Integrin α8β1 and several additional RGD-binding integrins bind nephronectin. Nephronectin mRNA is expressed in the ureteric bud epithelium, whereas α8β1 is expressed in the metanephric mesenchyme. Nephronectin is localized in the extracellular matrix in the same distribution as the ligand detected by α8β1-AP and forms a complex with α8β1 in vivo. Thus, these results strongly suggest that nephronectin is a relevant ligand mediating α8β1 function in the kidney. Nephronectin is expressed at numerous sites outside the kidney, so it may also have wider roles in development. The approaches used here should be generally useful for characterizing the interactions of novel extracellular matrix proteins identified through genomic sequencing projects.
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spelling pubmed-21507622008-05-01 Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney Brandenberger, Ralph Schmidt, Andrea Linton, James Wang, Denan Backus, Carey Denda, Sumiko Müller, Ullrich Reichardt, Louis F. J Cell Biol Research Articles The epithelial–mesenchymal interactions required for kidney organogenesis are disrupted in mice lacking the integrin α8β1. None of this integrin's known ligands, however, appears to account for this phenotype. To identify a more relevant ligand, a soluble integrin α8β1 heterodimer fused to alkaline phosphatase (AP) has been used to probe blots and cDNA libraries. In newborn mouse kidney extracts, α8β1-AP detects a novel ligand of 70–90 kD. This protein, named nephronectin, is an extracellular matrix protein with five EGF-like repeats, a mucin region containing a RGD sequence, and a COOH-terminal MAM domain. Integrin α8β1 and several additional RGD-binding integrins bind nephronectin. Nephronectin mRNA is expressed in the ureteric bud epithelium, whereas α8β1 is expressed in the metanephric mesenchyme. Nephronectin is localized in the extracellular matrix in the same distribution as the ligand detected by α8β1-AP and forms a complex with α8β1 in vivo. Thus, these results strongly suggest that nephronectin is a relevant ligand mediating α8β1 function in the kidney. Nephronectin is expressed at numerous sites outside the kidney, so it may also have wider roles in development. The approaches used here should be generally useful for characterizing the interactions of novel extracellular matrix proteins identified through genomic sequencing projects. The Rockefeller University Press 2001-07-23 /pmc/articles/PMC2150762/ /pubmed/11470831 http://dx.doi.org/10.1083/jcb.200103069 Text en Copyright © 2001, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Brandenberger, Ralph
Schmidt, Andrea
Linton, James
Wang, Denan
Backus, Carey
Denda, Sumiko
Müller, Ullrich
Reichardt, Louis F.
Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney
title Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney
title_full Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney
title_fullStr Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney
title_full_unstemmed Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney
title_short Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney
title_sort identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150762/
https://www.ncbi.nlm.nih.gov/pubmed/11470831
http://dx.doi.org/10.1083/jcb.200103069
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