Trafficking of CD82 and CD63 tetraspanins

描述(申请人提供)：Tetraspanins是一个在不同组织中表达的蛋白质家族，存在于许多物种中，但其生化功能仍然是个谜。它们相互之间以及与其他跨膜蛋白形成复合体的能力导致了一种假设，即它们可能参与膜结构和组织，和/或可能作为连接物发挥作用，在细胞外募集膜分子，在细胞内募集信号分子。对与Tetraspanins相互作用的蛋白质的表征表明，它们也参与了更专门的细胞过程，尽管对它们的离散功能的了解有限。Tetraspanin家族的两个成员CD82和CD63的表达动力学提示，它们在控制增殖、分化和迁移方面发挥了作用，所有这些过程都是肿瘤发生的核心。CD82和CD63的表达与肿瘤转移潜能呈负相关，进一步证实了CD82和CD63在肿瘤中的潜在重要性。本项目的目标是通过使用小鼠模型研究CD82和CD63的精确亚细胞定位和分子关联，从而深入了解CD82和CD63在免疫学背景下的功能，其中CD82和CD63的同源物已经被确定，但关于它们的行为和功能的数据仍然很少。对这些Tetraspanins功能的定义可能会导致新的癌症治疗方法的开发，以及可以想象的，癌症疫苗的合理设计。

DESCRIPTION (provided by applicant): Tetraspanins are a family of proteins expressed across different tissues and present in many species, but whose biochemical functions remain enigmatic. Their ability to form complexes with each other and other transmembrane proteins has led to the hypothesis that they may be involved in membrane structure and organization and/or may function as linkers, recruiting membrane molecules extracellularly and signaling molecules intracellularly. Characterization of proteins interacting with tetraspanins suggests their involvement in more specialized cell processes as well, although understanding of their discrete functions is limited. Expression kinetics of CD82 and CD63, two members of the tetraspanin family, hint at a role in the control of proliferation, differentiation and migration, all processes central to tumorigenesis. The potential importance of CD82 and CD63 in cancer is further substantiated by the inverse correlation existing between their expression and the metastatic potential of tumors. The goal of this project is to gain insight into the function of CD82 and CD63 in the immunological context by studying their precise subcellular localization and molecular associations using a mouse model, wherein CD82 and CD63 homologues have been identified but data on their behavior and function remain scarce. A definition of the function of these tetraspanins may lead to the development of new cancer treatments and, conceivably, the rational design of cancer vaccines.