Abstract
The small GTPase Rap1 induces integrin-mediated adhesion and changes in the actin cytoskeleton. The mechanisms that mediate these effects of Rap1 are poorly understood. We have identified RIAM as a Rap1-GTP-interacting adaptor molecule. RIAM defines a family of adaptor molecules that contain a RA-like (Ras association) domain, a PH (pleckstrin homology) domain, and various proline-rich motifs. RIAM also interacts with Profilin and Ena/VASP proteins, molecules that regulate actin dynamics. Overexpression of RIAM induced cell spreading and lamellipodia formation, changes that require actin polymerization. In contrast, RIAM knockdown cells had reduced content of polymerized actin. RIAM overexpression also induced integrin activation and cell adhesion. RIAM knockdown displaced Rap1-GTP from the plasma membrane and abrogated Rap1-induced adhesion. Thus, RIAM links Rap1 to integrin activation and plays a role in regulating actin dynamics.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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COS Cells
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Cell Adhesion
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Cell Adhesion Molecules / metabolism*
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Cell Line
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Chlorocebus aethiops
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Contractile Proteins / metabolism*
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Glutathione Transferase / metabolism
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Humans
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Integrins / metabolism
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Jurkat Cells
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Ligands
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Luciferases / metabolism
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Membrane Proteins
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Microfilament Proteins / metabolism*
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Molecular Sequence Data
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Phosphoproteins / metabolism*
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Profilins
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Proline / chemistry
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Protein Conformation
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Protein Structure, Tertiary
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Pseudopodia / metabolism
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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rap1 GTP-Binding Proteins / chemistry
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rap1 GTP-Binding Proteins / genetics
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rap1 GTP-Binding Proteins / metabolism*
Substances
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APBB1IP protein, human
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Actins
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Adaptor Proteins, Signal Transducing
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Cell Adhesion Molecules
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Contractile Proteins
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Evl protein, mouse
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Integrins
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Ligands
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Membrane Proteins
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Microfilament Proteins
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PFN1 protein, human
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Phosphoproteins
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Profilins
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Recombinant Fusion Proteins
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vasodilator-stimulated phosphoprotein
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Proline
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Luciferases
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Glutathione Transferase
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rap1 GTP-Binding Proteins