Trafficking of CD82 and CD63 tetraspanins

CD82 和 CD63 四跨膜蛋白的贩运

• 批准号: 6738755
• 负责人: KATERINA G ARTAVANIS-TSAKONAS
• 金额: $ 4.3万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6738755
• 关键词: CD antigens; MHC class II antigen; antigen presentation; cell differentiation; cell migration; cell proliferation; genetically modified animals; laboratory mouse; membrane activity; membrane proteins; postdoctoral investigator; protein localization; protein structure function; protein transport; tetraspanin; tissue /cell culture

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.

描述（由申请人提供）：四跨膜蛋白是在不同组织中表达并存在于许多物种中的蛋白质家族，但其生化功能仍然是个谜。它们与彼此和其他跨膜蛋白形成复合物的能力导致了这样的假设，即它们可能参与膜结构和组织和/或可能作为接头起作用，在细胞外募集膜分子和在细胞内募集信号分子。与四跨膜蛋白相互作用的蛋白质的表征表明它们也参与更专门的细胞过程，尽管对其离散功能的理解是有限的。四跨膜蛋白家族的两个成员CD 82和CD 63的表达动力学暗示了在控制增殖、分化和迁移中的作用，所有这些过程都是肿瘤发生的核心。CD 82和CD 63在癌症中的潜在重要性进一步被它们的表达与肿瘤的转移潜力之间存在的负相关性所证实。该项目的目标是通过使用小鼠模型研究其精确的亚细胞定位和分子关联来深入了解CD 82和CD 63在免疫学背景下的功能，其中CD 82和CD 63同源物已被鉴定，但关于其行为和功能的数据仍然很少。这些四跨膜蛋白的功能的定义可能会导致新的癌症治疗的发展，可以想象，癌症疫苗的合理设计。