Endocytic Crosstalk: Cavins, Caveolins, and Caveolae Regulate Clathrin-Independent Endocytosis

Abstract

Author SummaryEndocytosis is the process that allows cells to take up molecules from the environment. Several endocytic pathways exist in mammalian cells. While the best understood endocytic pathway uses clathrin, recent years have seen a great increase in our understanding of clathrin-independent endocytic pathways. Here we characterize the crosstalk between caveolae, flask-shaped specialized microdomains present at the plasma membrane, and a second clathrin-independent pathway, the CLIC/GEEC Cdc42-regulated endocytic pathway. These pathways are segregated in migrating cells with caveolae at the rear and CLIC/GEEC endocytosis at the leading edge. Here we find that specific caveolar proteins, caveolins and cavins, can also negatively regulate the CLIC/GEEC pathway. With the help of several techniques, including quantitative electron microscopy analysis and real-time live-cell imaging, we demonstrate that expression of caveolar proteins affects early carrier formation, causes cellular lipid changes, and changes the activity of the key regulator of the CLIC/GEEC pathway, Cdc42. The functional consequences of loss of caveolar proteins on the CLIC/GEEC pathway included inhibition of polarized cell migration and increased endocytosis in tissue explants.