Endophilin/SH3p4 is required for the transition from early to late stages in clathrin-mediated synaptic vesicle endocytosis

Endophilin/SH3p4 is a protein highly enriched in nerve terminals that binds the GTPase dynamin and the polyphosphoinositide phosphatase synaptojanin, two proteins implicated in synaptic vesicle endocytosis. We show here that antibody-mediated disruption of endophilin function in a tonically stimulat ed synapse leads to a block in the invagination of clathrin-coated pits adj acent to the active zone and therefore to a block of synaptic vesicle recyc ling. Mle also show that in a cell-free system, endophilin is not associate d with clathrin coats and is a functional partner of dynamin. Our findings suggest that endophilin is part of a biochemical machinery that acts in tra ns to the clathrin coat from early stages to vesicle fission.