title: Conformational activation of talin by RIAM triggers integrin-mediated cell adhesion.
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.
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Developmental Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Jamila
authors.initials: J
authors.lastname: Hirbawi
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Dwivedi
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Byzova
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Plow
authors.affiliation: Developmental Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D003412:Cricetulus; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016608:Talin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C521189:RIAM protein, mouse; D011994:Recombinant Proteins; D016608:Talin; C496077:Tln1 protein, mouse