Palmitoylated caveolin-1 enables endosome sorting of complex sphingolipids.

Complex sphingolipids form in the Golgi apparatus and require transport by vesicular carriers to reach the plasma membrane (PM) where they assemble with cholesterol to affect membrane function. The caveolin proteins have been implicated in sphingolipid trafficking but by mechanisms unknown. Here, we found that cells lacking caveolin-1 (Cav1) distributed the complex sphingolipids to the lysosome rather than to the PM. This was not seen in Cavin-1 KO cells, implicating a function for Cav1 independent of caveolae. The defect in trafficking localized to the sorting endosome where the complex sphingolipids failed to enter recycling tubules serving the PM. Sphingolipid trafficking was rescued by over-expression of Cav1, but not by a Cav1 mutant that lacked the S-palmitoylation sites. Thus, noncaveolar and palmitoylated Cav1 appears to act as a chaperone, or selectivity filter, enabling entry of the complex sphingolipids into endocytic recycling tubules to shape the composition of the PM.