| Vesicle trafficking is important for many cellular processes, from neurotransmitter release to plasma membrane lipid addition. Many proteins involved in vesicle trafficking have been identified. These include proteins associated with the vesicles, including synaptobrevins and rab GTP-binding proteins; and proteins on the acceptor membrane, such as syntaxins. Each of these proteins has a Drosophila homologue. I have undertaken a genetic analysis of the function of synaptobrevin, neuronal-synaptobrevin, syntaxin1, and drab3 in Drosophila vesicle trafficking.;Synaptobrevin is widely expressed gene. Three mutations have been identified in the gene and the phenotype is under study. Vesicle trafficking in many tissues appears to be effected. Neuronal-synaptobrevin was identified as a neuron specific isoform of the protein. Mutations induced by P-element insertions have been generated. These appear to eliminate evoked neurotransmitter release.;Syntaxin1 is present on the acceptor membrane in vesicle trafficking. It is expressed not only in the nervous system, but also in the early embryo. There syntaxin1 is necessary for the cellularization of the syncytial blastocyst. However, this effect is masked by maternally contributed syntaxin1, which must be eliminated by the generation of female germ line mosaics to study the phenotype.;Finally, drab3 is a small GTP-binding protein associated with synaptic vesicles. An attempt to mutagenize drab3 yielded mutations in an interacting gene, the lethality of which is suppressed by the expression of drab3. This gene is therefore termed suppressed-by-rab3 (sbr). Sbr has a synaptic phenotype similar to rab3A mutant mice. Postsynaptic responsiveness is normal, but rapid stimulation quickly fatigues the synapse and results in greatly reduced excitatory junctional currents. As a result, the mutants are nearly paralyzed and die without hatching from their egg cases.;Each of these proteins, therefore, is important for some form of vesicle trafficking in Drosophila. Neuronal-synaptobrevin functions at the synapse, while synaptobrevin functions in many tissues. Syntaxin1 functions both at the synapse and in early development, suggesting an interaction with both synaptobrevin genes. Lastly, a gene that interacts with drab3 shows a synaptic phenotype, however, its range of function cannot be assessed until it is cloned. |
