FCHo Proteins Are Nucleators of Clathrin-Mediated Endocytosis

Abstract

Initiator for Coated Pit Assembly During clathrin-mediated endocytosis, it has been thought that the sensing and binding of the clathrin adaptor protein AP2 to cargo and lipids leads to the recruitment of clathrin, nucleating the formation of a clathrin-coated pit. Henne et al. (p. 1281 , published online 6 May) have now found that this process of AP2 binding may not in fact represent either the first or the nucleation event of endocytosis. Instead, ubiquitous proteins called FCHo1/2 (F-BAR proteins) bind to the plasma membrane and define the sites of endocytosis independently of AP2. The F-BAR protein can generate very low curvature and, at higher concentration, generates higher curvature like those required at the neck of budding vesicles. The C terminus of the protein has a mu-homology domain (with homology to the mu domain of the AP2 complex) that interacts with Eps15 and intersectin, and via these proteins recruits AP2, which further recruits clathrin. Thus, a curvature-inducing protein can act to nucleate clathrin-coated pit assembly during endocytosis.