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

Jun Yang; Liang Zhu; Hao Zhang; Jamila Hirbawi; Koichi Fukuda; Pallavi Dwivedi; Jianmin Liu; Tatiana Byzova; Edward F Plow; Jinhua Wu; Jun Qin

doi:10.1038/ncomms6880

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

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

Authors

Affiliations

¹ Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
² 1] Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA [2] Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA.
³ Developmental Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA.

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
Tln1 protein, mouse

Associated data

PDB/2MWN

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding