Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating

Synaptic vesicle biogenesis involves the recycling of synaptic vesicle comp onents by clathrin-mediated endocytosis from the presynaptic membrane, ston ed 8, a protein encoded by the stoned locus in Drosophila melanogaster has been shown to regulate vesicle recycling by interacting with synaptotagmin. We report here the identification and characterization of a human homolog of stoned 8 (hStnB). Human stoned B is a brain-specific protein which co-en riches with other endocytic proteins such as AP-2 in a crude synaptic vesic le fraction and at nerve terminals. A domain with homology to the medium ch ain of adaptor complexes binds directly to both AP-2 and synaptotagmin and competes with AP-2 for the same binding site within synaptotagmin. Finally we show that the mu2 homology domain of hStnB stimulates the uncoating of b oth clathrin and AP-2 adaptors from clathrin-coated vesicles. We hypothesiz e that hStnB regulates synaptic vesicle recycling by facilitating vesicle u ncoating.