Trafficking of CD82 and CD63 tetraspanins

Harvard University (Medical School), Boston MA

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Abstract

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.