Yeast Eps15-like endocytic protein, Pan1p, activates the Arp2/3 complex

Longstanding evidence supports a role for actin in endocytosis; an intact a ctin cytoskeleton is required for endocytosis in yeast, and drugs that inhi bit actin polymerization inhibit endocytosis in both yeast and mammalian ce lls, The yeast Arp2/3 complex is required for the internalization step of e ndocytosis, In addition, some early endocytic events in mammalian cells are associated with the formation of actin tails similar to those generated by activated Arp2/3 complex. However, until now no Arp2/3 complex activator h as been identified among proteins known to mediate early steps in endocytos is, Here we show that the yeast endocytic protein Pan1p binds to and activa tes the Arp2/3 complex, Genetic interactions between PAN1 and mutants of Ar p2/3 subunits, or of the Arp2/3 activator LAS17, provide evidence for this activity in vivo. We suggest that Pan1p forms the core of an endocytic comp lex and physically couples actin polymerization nucleated by the Arp2/3 com plex to the endocytic machinery, thus providing the forces necessary for en docytosis.