CAVEOLIN FORMS A HETEROOLIGOMERIC PROTEIN COMPLEX THAT INTERACTS WITHAN APICAL GPI-LINKED PROTEIN - IMPLICATIONS FOR THE BIOGENESIS OF CAVEOLAE

Glycosyl-phosphatidylinositol (GPI)-linked proteins are transported to the apical surface of epithelial cells where they undergo cholesterol -dependent clustering in membrane micro-invaginations, termed caveolae or plasmalemmal vesicles. However, the sorting machinery responsible for this caveolar-clustering mechanism remains unknown. Using transfec ted MDCK cells as a model system, we have identified a complex of cell surface molecules (80, 50, 40, 22-24, and 14 kD) that interact in a p H- and cholesterol-dependent fashion with an apical recombinant GPI-li nked protein. A major component of this hetero-oligomeric protein comp lex is caveolin, a type II transmembrane protein. As this hetero-oligo meric caveolin complex is detectable almost immediately after caveolin synthesis, our results suggest that caveolae may assemble intracellul arly during transport to the cell surface. As such, our studies have i mplications for understanding both the intracellular biogenesis of cav eolae and their subsequent interactions with GPI-linked proteins in ep ithelia and other cell types.