Is Clathrin Required for Bulk Endocytosis

Key features of clathrin-associated endocytosis are outlined, and current evidence in favor of clathrin-independent endocytosis and of its structural counterpart(s) is reviewed. We next summarize our recent observations on clathrin-independent endocytosis in primary cultures of rat foetal fibroblasts, using two reversible inhibitors of the formation of endocytic clathrin-coated pits, Severe inhibition of clathrin polymerization at the plasma membrane slows down receptor-mediated endocytosis of transferrin by ten-fold, without affecting bulk-flow endocytosis of fluid and membrane. Furthermore, the size of primary endocytic vesicles, identified by ultrastructural cytochemistry; is the same in control and treated cells. Two interpretations are offered. The most provocative one proposes that clathrin plays no role in the formation of primary endocytic vesicles, and is only required to concentrate receptors in endocytic pits, accelerating thereby internalization of ligand-receptor complexes. In the second interpretation, inhibition of clathrin polymerization unmasks an accessory molecular machinery, which is not operating under control conditions. In both cases, another endocytic molecular machinery is required and remains to be identified.