Title: Vesicle-associated membrane protein and synaptophysin are associated on the synaptic vesicle.
Abstract: The synaptic vesicle membrane protein VAMP (yesicle-associated membrane protein or synaptobrevin) has been implicated in synaptic vesicle docking and fusion.Synaptophysin (p38), also a synaptic vesicle membrane protein, has four transmembrane domains and may function as a gap junction-like pore or channel.Here we report evidence for a direct interaction between VAMP and synaptophysin using chemical cross-linking followed by the identification of immunoreactive protein complexes.A prominent complex of 56 kDa was found to consist of VAMP and synaptophysin.Furthermore, we demonstrate that this VAMP-synaptophysin complex is enriched in the synaptic vesicle fraction of rat brain, is independent of detergent solubilization, and is present in PC12 cells subjected to in vivo cross-linking.The basis of chemical neurotransmission is the regulated secretion of neurotransmitter by synaptic vesicle-mediated exocytosis.Efforts to understand the molecular mechanism of this process have included the identification and characterization of the protein constituents of the synaptic vesicle membrane.These proteins are likely to be central mediators of the functions of synaptic vesicles, including biogenesis, docking, fusion, and recycling within nerve terminals.Additional synaptic vesicle proteins have served as tools to identify interacting proteins in the cytosol and nerve terminal membrane.It has recently become apparent that many of the proteins involved in synaptic vesicle trafficking have homologs involved in intracellular vesicular trafficking in a variety of systems.While synaptic vesicle trafficking utilizes components necessary for the intracellular vesicular trafficking of a wide variety of vesicles, it must also have specialized components that allow neurosecretion to occur in a regulated fashion with extreme rapidity and calcium dependence.A 7 S complex of proteins has been isolated which includes 1) the synaptic vesicle proteins, 2 ) VAMP,' synaptotagmin, and the plasma membrane proteins, and 3) syntaxin and synapse-associated protein 25.Three of and NIGMS, National Institutes of Health.The costs of publication of