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© The Rockefeller University Press, 0021-9525/2000//1075 $5.00
The Journal of Cell Biology, Volume 148, Number 5, , 2000 1075-1090

Integrin Dynamics and Matrix Assembly

: Tensin-Dependent Translocation of ₅β₁ Integrins Promotes Early Fibronectin Fibrillogenesis

Roumen Pankov^a, Edna Cukierman^a, Ben-Zion Katz^a, Kazue Matsumoto^a, Diane C. Lin^b, Shin Lin^b, Cornelia Hahn^a, and Kenneth M. Yamada^a

^a Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4370
^b Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California 92697-1450
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 421, 30 Convent Drive MSC 4370, Bethesda, MD 20892-4370.(301) 402-0897(301) 496-9124

ky4w{at}nih.gov

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 _vβ₃ remains within focal contacts, the fibronectin receptor ₅β₁ 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 µm/h and is independent of cell migration. It is induced by ligation of ₅β₁ integrins and depends on interactions with a functional actin cytoskeleton and vitronectin receptor ligation. During cell spreading, translocation of ligand-occupied ₅β₁ 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 ₅β₁ 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.

Key Words: fibronectin • integrin • tensin • vitronectin • extracellular matrix

© 2000 The Rockefeller University Press

Abbreviations used in this paper: ECM, extracellular matrix; FC, focal contacts; FN, fibronectin; GFP, green fluorescent protein; HFF, human foreskin fibroblasts; VN, vitronectin.

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