Integrin dynamics and matrix assembly:: Tensin-dependent translocation of α5β1 integrins promotes early fibronectin fibrillogenesis

被引:377
作者
Pankov, R
Cukierman, E
Katz, BZ
Matsumoto, K
Lin, DC
Lin, S
Hahn, C
Yamada, KM
机构
[1] Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA
[2] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA
关键词
fibronectin; integrin; tensin; vitronectin; extracellular matrix;
D O I
10.1083/jcb.148.5.1075
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 mu m/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.
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页码:1075 / 1090
页数:16
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