Membrane Distribution and Mobility of DC-SIGN

描述(申请人提供)：树突状细胞(DC)是免疫反应中的关键抗原提呈细胞，DC-SIGN是DC表达的一种抗原捕获受体。DC-SIGN介导的抗原捕获和内化过程是HIV-1病毒向T细胞传播的一种方式，而DC-SIGN是DC介导的T细胞“反式”感染所必需的。有趣的是，膜DC-SIGN以连接无关的方式形成100-200 nm的簇，这些结构被认为是有效结合-120 nm直径的HIV-1病毒粒子所必需的高亲和力结合部位。然而，DC-SIGN在活细胞上的聚集及其膜动力学还需要进一步的表征。由于DC-SIGN在HIV-1反式感染T细胞中的重要性，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DC-SIGN簇和单个蛋白在活树突状细胞中的膜分布和迁移率将是非常重要的。我们的工作集中在1)膜DC-SIGN在质膜上的聚集和迁移的生物物理特征，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.