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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA105862-02
Application #
6889517
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Lohrey, Nancy
Project Start
2004-05-01
Project End
2005-08-31
Budget Start
2005-05-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$14,888
Indirect Cost
Name
Harvard University
Department
Pathology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Artavanis-Tsakonas, Katerina; Kasperkovitz, Pia V; Papa, Eliseo et al. (2011) The tetraspanin CD82 is specifically recruited to fungal and bacterial phagosomes prior to acidification. Infect Immun 79:1098-106
Frickel, Eva-Maria; Quesada, Victor; Muething, Larissa et al. (2007) Apicomplexan UCHL3 retains dual specificity for ubiquitin and Nedd8 throughout evolution. Cell Microbiol 9:1601-10
Vyas, Jatin M; Kim, You-Me; Artavanis-Tsakonas, Katerina et al. (2007) Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells. J Immunol 178:7199-210
Artavanis-Tsakonas, Katerina; Love, J Christopher; Ploegh, Hidde L et al. (2006) Recruitment of CD63 to Cryptococcus neoformans phagosomes requires acidification. Proc Natl Acad Sci U S A 103:15945-50