The mechanical integrin cycle

Eileen Puklin-Faucher,Michael P Sheetz

doi:10.1242/jcs.042127

Abstract

Cells govern tissue shape by exerting highly regulated forces at sites of matrix adhesion. As the major force-bearing adhesion-receptor protein, integrins have a central role in how cells sense and respond to the mechanics of their surroundings. Recent studies have shown that a key aspect of mechanotransduction is the cycle by which integrins bind to the matrix at the leading cell edge, attach to the cytoskeleton, transduce mechanical force, aggregate in the plasma membrane as part of increasingly strengthened adhesion complexes, unbind and, ultimately, are recycled. This mechanical cycle enables the transition from early complexes to larger, more stable adhesions that can then rapidly release. Within this mechanical cycle, integrins themselves exhibit intramolecular conformational change that regulates their binding affinity and may also be dependent upon force. How the cell integrates these dynamic elements into a rigidity response is not clear. Here, we focus on the steps in the integrin mechanical cycle that are sensitive to force and closely linked to integrin function, such as the lateral alignment of integrin aggregates and related adhesion components.

Highlights

The mechanical integrin cycleThere was an error published in J
Cells shape tissues by pulling on neighboring cells and extracellular matrices (ECMs), creating specific levels of tension
Whereas Src has been shown to colocalize with αVβ3- but not α5β1-integrins (Felsenfeld et al, 1999), evidence of regulation of syndecan 4 by focal adhesion kinase (FAK) is robust. These findings suggest that, similar to focal-adhesion strengthening through talin crosslinking across linearly arranged αVβ3 and α5β1 integrins, focal-adhesion turnover can be regulated by the linear arrangement of αVβ3- and α5β1-integrin, in synergy with syndecan 1 and syndecan 4, and crosslinked inside and outside the cell by the FAK-Src complex and fibronectin module, respectively

Summary

The mechanical integrin cycle

There was an error published in J. Recent studies have shown that a key aspect of mechanotransduction is the cycle by which integrins bind to the matrix at the leading cell edge, attach to the cytoskeleton, transduce mechanical force, aggregate in the plasma membrane as part of increasingly strengthened adhesion complexes, unbind and, are recycled. This mechanical cycle enables the transition from early complexes to larger, more stable adhesions that can rapidly release.

Introduction

Conclusions and perspectives