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PMID: 10704455 Published · ppublish English Journal Article

Integrin dynamics and matrix assembly: tensin-dependent translocation of alpha(5)beta(1) integrins promotes early fibronectin fibrillogenesis.

The Journal of cell biology ·Vol. 148 ·No. 5 ·2000-03-06 ·Pages 1075-90

Pankov R, Cukierman E, Katz BZ, Matsumoto K, Lin DC, Lin S, Hahn C, Yamada KM

Abstract

Fibronectin matrix assembly is a multistep, integrin-dependent process. To investigate the role of integrin dynamics in fibronectin fibrillogenesis, we developed an antibody-chasing technique for simultaneous tracking of two integrin populations by different antibodies. We established that whereas the vitronectin receptor alpha(v)beta(3) remains within focal contacts, the fibronectin receptor alpha(5)beta(1) translocates from focal contacts into and along extracellular matrix (ECM) contacts. This escalator-like translocation occurs relative to the focal contacts at 6.5 +/- 0.7 microm/h and is independent of cell migration. It is induced by ligation of alpha(5)beta(1) integrins and depends on interactions with a functional actin cytoskeleton and vitronectin receptor ligation. During cell spreading, translocation of ligand-occupied alpha(5)beta(1) integrins away from focal contacts and along bundles of actin filaments generates ECM contacts. Tensin is a primary cytoskeletal component of these ECM contacts, and a novel dominant-negative inhibitor of tensin blocked ECM contact formation, integrin translocation, and fibronectin fibrillogenesis without affecting focal contacts. We propose that translocating alpha(5)beta(1) integrins induce initial fibronectin fibrillogenesis by transmitting cytoskeleton-generated tension to extracellular fibronectin molecules. Blocking this integrin translocation by a variety of treatments prevents the formation of ECM contacts and fibronectin fibrillogenesis. These studies identify a localized, directional, integrin translocation mechanism for matrix assembly.

MeSH Terms
Biological Transport/drug effects Cell Membrane/metabolism Cells, Cultured Cytoskeleton/metabolism Dimerization Extracellular Matrix/metabolism Fibroblasts/cytology,metabolism Fibronectins/biosynthesis Green Fluorescent Proteins Humans Integrin beta1/metabolism Ligands Luminescent Proteins/genetics Microfilament Proteins/genetics,metabolism,pharmacology Peptide Fragments/biosynthesis,genetics,pharmacology Protein Structure, Tertiary/genetics Receptors, Fibronectin/metabolism Receptors, Vitronectin/metabolism Recombinant Fusion Proteins/biosynthesis,genetics,pharmacology Tensins Transfection
Chemicals
Fibronectins Integrin beta1 Ligands Luminescent Proteins Microfilament Proteins Peptide Fragments Receptors, Fibronectin Receptors, Vitronectin Recombinant Fusion Proteins Tensins Green Fluorescent Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Pankov R
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA.
Cukierman E
Katz B Z
Matsumoto K
Lin D C
Lin S
Hahn C
Yamada K M
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.148.5.1075
Published
2000-03-06
Pages
1075-90
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2174533
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.148.5.1075 PMC Full Text View journal details
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