The structure of synaptobrevin, an intrinsic membrane protein of small synaptic vesicles from mammalian brain, was studied by purification and molecular cloning. Its message in bovine brain encodes a 116 amino acid protein whose sequence reveals it to be the mammalian homolog of Torpedo VAMP-l. Antibody probing demonstrates that the protein is also present in Drosophila, and its Drosophila homolog was cloned. Alignment of the sequences of synaptobrevin/VAMP-1 from the three species shows it to contain four domains, including a highly conserved central region of 63 amino acids that contains 75% invariant residues. The finding that a membrane protein from vertebrate synaptic vesicles is conserved in Drosophila points toward a central role of this protein in neurotransmission and should allow a genetic approach to neurotransmitter release. introduction

Small synaptic vesicles are characteristic components of presynaptic nerve terminals. Here they represent a specialized organelle that has a central function in the uptake, storage, and release of neurotransmitters such as acetylcholine and glutamate(Ceccarelli and Hurlbut, 1980). All small synaptic vesicles appear to follow the same intracellular pathways in neurons and may be subject to similar intracellular regulatory mechanisms. Synaptic vesicle assembly, sorting, and exo-endocytotic recycling constitute basic features of neurons in all animal species that are independent of the neurotransmitter which they contain. It is probable that small synaptic vesicles share a set of proteins that determine these common pathways and their regulation(Kelly, 1988). Vertebrate and invertebrate synapses are very similar to each other morphologically and electrophysiologically. If these similarities extend to the biochemical events leading to neurotransmitter release, one would expect to find homologous proteins at homologous positions in the intracellular pathway of synaptic vesicles mediating such general functions. It is therefore of great importance to identify the major proteins common to all synaptic vesicles and, in particular, the proteins that are