Expression of caveolin-1 is required for the transport of caveolin-2 to the plasma membrane - Retention of caveolin-2 at the level of the Golgi complex

Caveolins-1 and -2 are normally co-expressed, and they form a hetero-oligom eric complex in many cell types. These caveolin hetero-oligomers are though t to represent the assembly units that drive caveolae formation in vivo. Ho wever, the functional significance of the interaction between caveolins-1 a nd -2 remains unknown. Here, we show that caveolin-1 co-expression is requi red for the transport of caveolin-2 from the Golgi complex to the plasma me mbrane. We identified a human erythroleukemic cell line, K562, that express es caveolin-2 but fails to express detectable levels of caveolin-1, This al lowed us to stringently assess the effects of recombinant caveolin-1 expres sion on the behavior of endogenous caveolin-2, We show that expression of c aveolin-1 in K562 cells is sufficient to reconstitute the de nov formation of caveolae in these cells. In addition, recombinant expression of caveolin -1 allows caveolin-2 to form high molecular mass oligomers that are targete d to caveolae-enriched membrane fractions. In striking contrast, in the abs ence of caveolin-1 expression, caveolin-2 forms low molecular mass oligomer s that are retained at the level of the Golgi complex. Interestingly, we al so show that expression of caveolin-1 in K562 cells dramatically up-regulat es the expression of endogenous caveolin-2, Northern blot analysis reveals that caveolin-2 mRNA levels remain constant under these conditions, suggest ing that the expression of caveolin-1 stabilizes the caveolin-2 protein. Co nversely, transient expression of caveolin-2 in CHO cells is sufficient to up-regulate endogenous caveolin-1 expression. Thus, the formation of a hete ro-oligomeric complex between caveolins-1 and -2 stabilizes the caveolin-2, protein product and allows caveolin-2 to be transported from the Golgi com plex to the plasma membrane.