title: CD28 inhibits T cell adhesion by recruiting CAPRI to the plasma membrane.
abstract: CD28 is a coreceptor expressed on T lymphocytes. Signaling downstream of CD28 promotes multiple T cell functions such as proliferation, survival, and cytokine secretion. Adhesion to APCs is another function of T cells; however, little is known with regard to the role of CD28 in this process. Our previous studies have shown that CD28 inhibits T cell adhesion, but the underlying mechanism that mediates this process remains unknown. In the present study we discovered that signaling downstream of CD28 resulted in inhibition of Rap1 activity and decreased LFA-1-mediated adhesion. We showed that this was regulated by the recruitment of calcium-promoted Ras inactivator (CAPRI), a GTPase-activating protein, to the plasma membrane downstream of CD28 signaling. CAPRI trafficking to the plasma membrane was secondary to calcium influx and was mediated by its C2A and C2B domains. We conclude that CD28 inhibits Rap1-mediated adhesion by recruiting the protein CAPRI to the plasma membrane.
authors: Department of Medicine, New York University School of Medicine, New York, NY 10016.
authors: Marianne
authors: M
authors: Strazza
authors: Department of Medicine, New York University School of Medicine, New York, NY 10016.
authors: Inbar
authors: I
authors: Azoulay-Alfaguter
authors: Department of Medicine, New York University School of Medicine, New York, NY 10016.
authors: Bryan
authors: B
authors: Dun
authors: Department of Medicine, New York University School of Medicine, New York, NY 10016.
authors: Jairo
authors: J
authors: Baquero-Buitrago
authors: Department of Medicine, New York University School of Medicine, New York, NY 10016 Adam.Mor@NYUMC.org.
authors: Adam
authors: A
authors: Mor
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D018106:CD28 Antigens / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D021381:Protein Transport / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; C504471:Rasa4 protein, mouse; D020703:ras GTPase-Activating Proteins; D049452:Green Fluorescent Proteins; D020827:rap1 GTP-Binding Proteins; D002118:Calcium