title: Non-cleavable talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1.
abstract: While the cytoskeletal protein talin binds to the β-chain of LFA-1, the immune cell adaptor SKAP1 (SKAP-55) binds to the α-chain of the same integrin via RapL. Whereas calpain protease cleavage of talin is important for LFA-1 activation, it has been unclear whether SKAP1 can alter the function of talin or its associated adaptor RIAM in T-cells. In this paper, we report that Skap1-/- T-cells showed a reduction in the translocation of talin and RIAM to the contact interface of T-cells with antigenic beads or dendritic cells (DCs) presenting OVA peptide to OT-1 T-cells. In addition, Skap1-/- T-cells show an altered pattern of talin cleavage, while the expression of a cleavage resistant form of talin (L432G) restored the impaired adhesion of OT1 transgenic Skap1-/- T-cells with DCs. SKAP1 therefore can affect the function of talin in T-cells needed for optimal T-cell/DC conjugation.
authors.affiliation: Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK; Cambridge Institute of Medical Research, Hills Road, CB2 OXY Cambridge, UK.
authors.forename: Daina
authors.initials: D
authors.lastname: Lim
authors.affiliation: Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK; Cambridge Institute of Medical Research, Hills Road, CB2 OXY Cambridge, UK.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK; Cambridge Institute of Medical Research, Hills Road, CB2 OXY Cambridge, UK. Electronic address: cer51@cam.ac.uk.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Rudd
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D054992:Immunological Synapses / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D059748:Proteolysis; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000502:physiology*; D016608:Talin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; D010750:Phosphoproteins; D016608:Talin; C521189:RIAM protein, mouse; C514255:SKAP1 protein, mouse
keywords: Adhesion; LFA-1; T-cells; Talin