Role of the CDM family proteins in the immune surveillance.

肌动蛋白细胞骨架的重塑是一种基本的生物反应，调节免疫系统中的各种细胞功能。这些包括吞噬作用、细胞迁移和抗原识别，所有这些都被认为在对病原体的免疫监视中发挥着重要作用。CDM家族蛋白是新发现的、进化上保守的Rho家族GTP酶鸟嘌呤核苷酸交换因子(GEF)。在本项目中，我们分析了CDM家族蛋白在免疫监测中的作用，特别是DOCK2。我们的主要发现如下：(1)。DOCK2位于TCR下游，通过激活RAC调节免疫突触的形成。DOCK2介导的RAC激活需要与ELMO1相互作用。DOCK2对T、B淋巴细胞归巢至次级淋巴器官的作用不同。DOCK2调控胸腺Va14 NKT细胞的发育。DOCK2缺乏使同种异体心脏移植物能够长期存活。DOCK2是一种RAC激活剂，调节中性粒细胞的迁移和超氧化物的产生。

Remodeling of the actin cytoskeleton is a fundamental biological response and regulates various cellular functions in the immune system. These include phagocytosis, cell migration and antigen recognition, all of which are known to play important roles in the immune surveillance against pathogens. The CDM family proteins are novel and evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho family GTPases. In this project, we have analyzed the role of the CDM family proteins in the immune surveillance, especially focusing on DOCK2. Our major findings are as follows :(1). DOCK2 functions downstream of TCR and regulates immunological synapse formation through Rac activation.(2). DOCK2-mediated Rac activation requires interaction with ELMO1.(3). DOCK2 differently contributes to homing of T and B lymphocytes to the secondary lymphoid organs.(4). DOCK2 regulates development of the Va14 NKT cells in the thymus.(5). DOCK2-deficiency enables long-term survival of cardiac allo-grafts.(6). DOCK2 is a Rac activator that regulates migration and superoxide production in neutrophils.