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Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins
The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2198870/ https://www.ncbi.nlm.nih.gov/pubmed/11706054 http://dx.doi.org/10.1083/jcb.200101099 |
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author | Mechtersheimer, Sabine Gutwein, Paul Agmon-Levin, Nancy Stoeck, Alexander Oleszewski, Matthias Riedle, Svenja Postina, Rolf Fahrenholz, Falk Fogel, Mina Lemmon, Vance Altevogt, Peter |
author_facet | Mechtersheimer, Sabine Gutwein, Paul Agmon-Levin, Nancy Stoeck, Alexander Oleszewski, Matthias Riedle, Svenja Postina, Rolf Fahrenholz, Falk Fogel, Mina Lemmon, Vance Altevogt, Peter |
author_sort | Mechtersheimer, Sabine |
collection | PubMed |
description | The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to αvβ5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by αvβ5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via αvβ5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions. |
format | Text |
id | pubmed-2198870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21988702008-05-01 Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins Mechtersheimer, Sabine Gutwein, Paul Agmon-Levin, Nancy Stoeck, Alexander Oleszewski, Matthias Riedle, Svenja Postina, Rolf Fahrenholz, Falk Fogel, Mina Lemmon, Vance Altevogt, Peter J Cell Biol Article The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to αvβ5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by αvβ5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via αvβ5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions. The Rockefeller University Press 2001-11-12 /pmc/articles/PMC2198870/ /pubmed/11706054 http://dx.doi.org/10.1083/jcb.200101099 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 | Article Mechtersheimer, Sabine Gutwein, Paul Agmon-Levin, Nancy Stoeck, Alexander Oleszewski, Matthias Riedle, Svenja Postina, Rolf Fahrenholz, Falk Fogel, Mina Lemmon, Vance Altevogt, Peter Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins |
title | Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins |
title_full | Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins |
title_fullStr | Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins |
title_full_unstemmed | Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins |
title_short | Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins |
title_sort | ectodomain shedding of l1 adhesion molecule promotes cell migration by autocrine binding to integrins |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2198870/ https://www.ncbi.nlm.nih.gov/pubmed/11706054 http://dx.doi.org/10.1083/jcb.200101099 |
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