title: Association of syntenin-1 with M-RIP polarizes Rac-1 activation during chemotaxis and immune interactions.
abstract: In this study, we describe that the PDZ protein syntenin-1 is a crucial element for the generation of signaling asymmetry during the cellular response to polarized extracellular cues. We analyze the role of syntenin-1 in the control of asymmetry in two independent models of T cell polarization--the migratory response to chemoattractants and the establishment of cognate interactions between T cells and antigen-presenting cells (APCs). A combination of mutant, biochemical and siRNA approaches demonstrate that syntenin-1 is vital for the generation of polarized actin structures such as the leading edge and the contact zone with APCs. We found that the mechanism by which syntenin-1 controls actin polymerization relies on its mandatory role for activation of the small GTPase Rac. Syntenin-1 controls Rac through a specific association with the myosin phosphatase Rho interacting protein (M-RIP), which occurs in response to phosphorylation of syntenin-1 by Src at Tyr4. Our data indicate the key role of syntenin-1 in the generation of functional asymmetry in T cells and provide a novel mechanistic link between receptor activation and actin polymerization and accumulation in response to extracellular stimulation.
authors.affiliation: Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029, Madrid,  Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Sala-Valdés
authors.forename: Mónica
authors.initials: M
authors.lastname: Gordón-Alonso
authors.forename: Emilio
authors.initials: E
authors.lastname: Tejera
authors.forename: Anna
authors.initials: A
authors.lastname: Ibáñez
authors.forename: J Román
authors.initials: JR
authors.lastname: Cabrero
authors.forename: Angeles
authors.initials: A
authors.lastname: Ursa
authors.forename: María
authors.initials: M
authors.lastname: Mittelbrunn
authors.forename: Francisco
authors.initials: F
authors.lastname: Lozano
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
mesh_terms: D000199:Actins / Q000096:biosynthesis; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D002460:Cell Line; D016764:Cell Polarity; D002634:Chemotaxis, Leukocyte; D006801:Humans; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D053676:Syntenins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C498552:MPRIP protein, human; D034741:RNA, Small Interfering; D053676:Syntenins; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein