Membrane Distribution and Mobility of DC-SIGN

描述（由申请人提供）：树突状细胞（DC）是免疫应答中的关键抗原呈递细胞，DC-SIGN是DC表达的抗原捕获受体。DC-SIGN介导的抗原捕获和内化过程被HIV-1用作病毒传播至T细胞的手段，DC-SIGN对于DC介导的T细胞“反式”感染是必需的。有趣的是，膜DC-SIGN以不依赖连接的方式形成100-200 nm簇，并且这些结构被认为代表有效结合~ 120 nm直径的HIV-1病毒体所必需的高亲合力结合位点。然而，DC-SIGN在活细胞上的聚集及其膜动力学需要进一步表征。由于DC-SIGN对于T细胞的HIV-1反式感染的重要性以及这些有组织的膜结构作为病毒结合和进入DC的端口的潜在作用，研究活DC中DC-SIGN簇和单个蛋白质的膜分布和移动性将是重要的。拟议的工作重点是1）膜DC-SIGN的生物物理表征，关于质膜上的簇和簇迁移率，以及2）可能解释DC-SIGN膜分布的潜在分子机制。

DESCRIPTION (provided by applicant): Dendritic Cells (DC) are key antigen presenting cells in the immune response, and DC-SIGN is an antigen capture receptor expressed by DC. The DC-SIGN mediated process of antigen capture and internalization is exploited by HIV-1 as a means of viral dissemination to T cells, and DC-SIGN is necessary for DC-mediated infection of T cells "in trans". Interestingly, membrane DC-SIGN forms 100-200 nm clusters in a ligation- independent manner, and these structures are thought to represent high avidity binding sites necessary for efficient binding of -120 nm diameter HIV-1 virions. However, the clustering of DC-SIGN on live cells and its membrane dynamics require further characterization. Due to the importance of DC-SIGN for HIV-1 trans- infection of T cells and the potential role of these organized membrane structures as ports for viral binding and entry into DC, it will be important to investigate the membrane distribution and mobility of DC-SIGN clusters and individual proteins in live DC. The proposed work focuses on 1) biophysical characterization of membrane DC-SIGN with respect to clustering and cluster mobility on the plasma membrane and 2) underlying molecular mechanisms that may account for the membrane distribution of DC-SIGN.