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

R. Pankov, E. Cukierman, B. Z. Katz, K. Matsumoto, D. C. Lin, S. Lin, C. Hahn, K. M. Yamada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 α(v)β3 remains within focal contacts, the fibronectin receptor α5β1 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 α5β1 integrins and depends on interactions with a functional actin cytoskeleton and vitronectin receptor ligation. During cell spreading, translocation of ligand-occupied α5β1 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 α5β1 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.

Original languageEnglish
Pages (from-to)1075-1090
Number of pages16
JournalJournal of Cell Biology
Volume148
Issue number5
DOIs
StatePublished - 6 Mar 2000
Externally publishedYes

Keywords

  • Extracellular matrix
  • Fibronectin
  • Integrin
  • Tensin
  • Vitronectin

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