Genetic dissection of the molecular mechanisms of transmitter vesicle release during synaptic transmission

Over the last few years there has been rapid progress in our understanding of the molecular mechanisms of synaptic transmission. This advance is largely due to the convergence of biochemical and genetic approaches to identify a discrete set of synaptic proteins associated with transmitter vesicles and their specialized fusion sites in the presynaptic membrane. The fruitfly, Drosophila melanogaster, is an attractive system to further such studies where we can combine sophisticated molecular genetic manipulations with direct observation of synaptic phenotypes at the well-characterized neuromuscular junction (NMJ). So far, five essential synaptic proteins have been identified in Drosophila and genetically modified or removed from the synapse: synaptotagmin, synaptobrevin (also called VAMP), syntaxin, Rop (Drosophila n-sec1 homologue) and cysteine string protein (csp). We are presently characterizing the functional roles of these identified proteins using electrophysiological and ultrastructural analyses of genetic mutants. In this article I review our current knowledge of these five proteins in Drosophila and discuss their possible functional roles in the molecular machinery governing synaptic transmission.