Conformational activation of talin by RIAM triggers integrin-mediated cell adhesion

Nat Commun. 2014 Dec 18;5:5880. doi: 10.1038/ncomms6880.

Abstract

The membrane localization and activation of cytoskeletal protein talin are key steps to initiate the integrin transmembrane receptors' activation, which mediates many cellular adhesive responses such as cell migration, spreading and proliferation. RIAM, a membrane anchor and small GTPase RAP1 effector, is known to bind to the C-terminal rod domain of talin (talin-R) and promote localizations of talin to the membrane. Through systematic mapping analysis, we find that RIAM also binds to the N-terminal head of talin (talin-H), a crucial domain involved in binding and activating integrins. We show that the RIAM binding to talin-H sterically occludes the binding of a talin-R domain that otherwise masks the integrin-binding site on talin-H. We further provide functional evidence that such RIAM-mediated steric unmasking of talin triggers integrin activation. Our findings thus uncover a novel role for RIAM in conformational regulation of talin during integrin activation and cell adhesion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • CHO Cells
  • Cell Adhesion
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Cricetulus
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Gene Expression Regulation
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Models, Molecular
  • Platelet Glycoprotein GPIIb-IIIa Complex / chemistry*
  • Platelet Glycoprotein GPIIb-IIIa Complex / genetics
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Protein Transport
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Talin / chemistry*
  • Talin / genetics
  • Talin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • RIAM protein, mouse
  • Recombinant Proteins
  • Talin
  • talin protein, mouse

Associated data

  • PDB/2MWN