An interaction between integrin and the talin FERM domain mediates integrin activation but not linkage to the cytoskeleton

Nat Cell Biol. 2006 Jun;8(6):601-6. doi: 10.1038/ncb1411. Epub 2006 Apr 30.

Abstract

Transmembrane adhesion receptors, such as integrins, mediate cell adhesion by interacting with intracellular proteins that connect to the cytoskeleton. Talin, one such linker protein, is thought to have two roles: mediating inside-out activation of integrins, and connecting extracellular matrix (ECM)-bound integrins to the cytoskeleton. Talin's amino-terminal head, which consists of a FERM domain, binds an NPxY motif within the cytoplasmic tail of most integrin beta subunits. This is consistent with the role of FERM domains in recruiting other proteins to the plasma membrane. We tested the role of the talin-head-NPxY interaction in integrin function in Drosophila. We found that introduction of a mutation that perturbs this binding in vitro into the isolated talin head disrupts its recruitment by integrins in vivo. Surprisingly, when engineered into the full-length talin, this mutation did not disrupt talin recruitment by integrins nor its ability to connect integrins to the cytoskeleton. However, it reduced the ability of talin to strengthen integrin adhesion to the ECM, indicating that the function of the talin-head-NPxY interaction is solely to regulate integrin adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Cytoskeleton / metabolism*
  • Drosophila
  • Drosophila Proteins / metabolism
  • Epithelial Cells / metabolism
  • Integrins / metabolism*
  • Mutagenesis, Site-Directed
  • Protein Binding / genetics
  • Talin / genetics
  • Talin / metabolism*
  • Wings, Animal / cytology

Substances

  • Drosophila Proteins
  • Integrins
  • Talin