Tetraspanins: Small transmembrane proteins with big impact on membrane microdomain structures.

Members of the tetraspanin family of transmembrane proteins including CD9, CD37, CD53, CD63, CD81, CD82, CD151, etc., contribute to the structural organization of the plasma membrane by forming microdomain structures, influencing cell fusion and regulating cell motility. Interestingly, K41, a CD9-specific monoclonal antibody (mAb), inhibits the release of human immunodeficiency virus (HIV-1), and the canine distemper virus (CDV)-, but not measles virus (MV)-induced cell-cell fusion. This mAb, which recognizes a conformational epitope on the large extracellular loop (LEL) of CD9, induced rapid relocation and clustering of CD9 in net-like structures at cell-cell contact areas.1 High-resolution analyses revealed that CD9 clustering is accompanied by the formation of microvilli that protrude from either side of adjacent cell surfaces, thus forming structures like microvilli zippers. While the cellular CD9-associated proteins beta1-integrin and EWI-F were co-clustered with CD9 at cell-cell interfaces, viral proteins in infected cells were differentially affected. MV envelope proteins were detected within, whereas CDV proteins were excluded from CD9 clusters, and thus, the tetraspanin CD9 can regulate cell-cell fusion by controlling the access of the viral fusion machinery to cell contact areas.