title: The Rap1-RIAM-talin axis of integrin activation and blood cell function.
abstract: Integrin adhesion receptors mediate the adhesion of blood cells, such as leukocytes, to other cells, such as endothelial cells. Integrins also are critical for anchorage of hematopoietic precursors to the extracellular matrix. Blood cells can dynamically regulate the affinities of integrins for their ligands ("activation"), an event central to their functions. Here we review recent progress in understanding the mechanisms of integrin activation with a focus on the functions of blood cells. We discuss how talin binding to the integrin β cytoplasmic domain, in conjunction with the plasma membrane, induces long-range allosteric rearrangements that lead to integrin activation. Second, we review our understanding of how signaling events, particularly those involving Rap1 small guanosine triphosphate (GTP)hydrolases, can regulate the talin-integrin interaction and resulting activation. Third, we review recent findings that highlight the role of the Rap1-GTP-interacting adapter molecule (RIAM), encoded by the APBB1IP gene, in leukocyte integrin activation and consequently in leukocyte trafficking.
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA; and.
authors.forename: Frederic
authors.initials: F
authors.lastname: Lagarrigue
authors.affiliation: Department of Life Sciences, Korea University, Seoul, South Korea.
authors.forename: Chungho
authors.identifier: 0000-0003-4343-6333
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA; and.
authors.forename: Mark H
authors.identifier: 0000-0002-5685-5417
authors.initials: MH
authors.lastname: Ginsberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D000072417:Protein Domains; D000089804:Shelterin Complex; D016608:Talin / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism*
chemical_list: C493340:APBB1IP protein, human; D048868:Adaptor Proteins, Signal Transducing; D016023:Integrins; D008565:Membrane Proteins; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D016608:Talin; D034501:Telomere-Binding Proteins