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.
Highlights
Integrins play central roles in mediating trans-endothelial migration of T-cells and their contact with antigen presenting cells (APCs) [1,2,3]
We have shown that SKAP1 is an effector is the inside-out pathway by interacting with RapL in T-cells [18,19,21,22,23,24]
We previously reported that SKAP1 was needed for LFA-1 adhesion and T-cell conjugation in response to super-antigen [18,20,23]
Summary
Integrins play central roles in mediating trans-endothelial migration of T-cells and their contact with antigen presenting cells (APCs) [1,2,3]. Phosphoprotein 1: HUGO official designation; SKAP-55, src kinase-associated phosphoprotein-55) are needed for 1 and 2 integrin activation [18,19,20]. We report that T-cells from Skap1−/− mice show altered processing and localization of talin in T-cells, concurrent with reduced dwell times with DCs, and further that a cleavage resistant L432G talin rescued impaired Skap1−/− T-cell conjugation. This observation finding demonstrates cross-regulation between SKAP1 and talin in T-cells despite binding to distinct chains of LFA-1
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