The Talin Head Domain Binds to Integrin β Subunit Cytoplasmic Tails and Regulates Integrin Activation

David A Calderwood,Roy Zent,Richard Grant,D Jasper G Rees,Richard O Hynes,Mark H Ginsberg

doi:10.1074/jbc.274.40.28071

Abstract

The beta subunit cytoplasmic domains of integrin adhesion receptors are necessary for the connection of these receptors to the actin cytoskeleton. The cytoplasmic protein, talin, binds to beta integrin cytoplasmic tails and actin filaments, hence forming an integrin-cytoskeletal linkage. We used recombinant structural mimics of beta(1)A, beta(1)D and beta(3) integrin cytoplasmic tails to characterize integrin-binding sites within talin. Here we report that an integrin-binding site is localized within the N-terminal talin head domain. The binding of the talin head domain to integrin beta tails is specific in that it is abrogated by a single point mutation that disrupts integrin localization to talin-rich focal adhesions. Integrin-cytoskeletal interactions regulate integrin affinity for ligands (activation). Overexpression of a fragment of talin containing the head domain led to activation of integrin alpha(IIb)beta(3); activation was dependent on the presence of both the talin head domain and the integrin beta(3) cytoplasmic tail. The head domain of talin thus binds to integrins to form a link to the actin cytoskeleton and can thus regulate integrin function.

Highlights

The connection of integrin adhesion receptors to the actin cytoskeleton regulates cell shape, adhesion, and migration [1]
In contrast to ERM proteins, previous studies indicate that the C-terminal rod domain of talin contains the integrin-binding site and the vinculin- and actin-binding sites [5, 6, 11]
We examined the interaction of the talin head domain with three of these integrin ␤ cytoplasmic tails and report that either recombinant or proteolytically derived talin head domains bind to all three ␤ tails

Summary

Introduction

The connection of integrin adhesion receptors to the actin cytoskeleton regulates cell shape, adhesion, and migration [1]. In contrast to ERM proteins, previous studies indicate that the C-terminal rod domain of talin contains the integrin-binding site and the vinculin- and actin-binding sites [5, 6, 11]. Overexpression of the talin fragments containing the head domain “activated” integrin ␣IIb␤3 as judged by increased ligand-binding affinity.

Results

Conclusion