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SLAT, a T Cell-Specific Signaling Protein

In 2003, we reported the isolation and initial characterization of a novel signaling protein, termed SWAP-70-Like Adaptor of T cells (SLAT; aka Def6), which is selectively expressed in T cells. Upon antigen stimulation, SLAT selectively localizes to the T cell IS, where it plays a key role in initiating cytoskeletal changes and Ca2+ signaling. As a result, T cells that are genetically deficient for SLAT display a severe defect in TCR-induced activation and differentiation into different Th subsets. Our more recent work has elucidated the mechanistic basis for the indispensable role of SLAT in T cell Ca2+ signaling by revealing that , following TCR triggering, SLAT directly binds to the ER-localized inositol triphosphate receptor (IP3R) and facilitates its Ca2+ ion channel function, which initiates Ca2+ signaling in T cells, the latter being required for productive T cell activation and effector functions.