Role of the CDM family protein DOCK2 in lymphocyte functions

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Remodeling of the actin cytoskeleton is a fundamental biological response that regulates various cellular functions in the immune system. For example, it is currently considered that phagocytosis of foreign antigens or apoptotic cells by macrophages, migration of lymphoid and myeloid cells, and immunological synapse formation in T cells are critically regulated by remodeling of the actin cytoskeleton, yet the molecular mechanism involved in this process is poorly understood.The CDM family proteins are the molecules conserved Caenorhabditis elegans, Drosophila melanogaster and mammals, and regulate remodeling of the actin cytoskeleton by functioning upstream of Rac. -We have identified DOCK2, a new member of the CDM family proteins, that is predominantly expressed in lymphocytes. By generating DOCK2-deficient mice, we demonstrated that DOCK2 functions downstream of chemokine receptors and T cell antigen receptor, and plays an important role in lymphocyte migration and immunological synapse formation through activation of Rac. In addition, we found that interaction of DOCK2 with ELMO1 is critical for Rac activation and cytoskeletal reorganization. Therefore, our findings suggest that DOCK2-ELMO1 interaction would b,e a novel molecular target for immune-related diseases caused by infiltration and activation of T cells.