SYNAPTIC TRANSMISSION PERSISTS IN SYNAPTOTAGMIN MUTANTS OF DROSOPHILA

Synaptotagmin is one of the major integral membrane proteins of synapt ic vesicles. It has been postulated to dock vesicles to their release sites, to act as the Ca2+ sensor for the release process, and to be a fusion protein during exocytosis. To clarify the function of this prot ein, we have undertaken a genetic analysis of the synaptotagmin gene i n Drosophila. We have identified five lethal alleles of synaptotagmin, at least one of which lacks detectable protein. Surprisingly, however , many embryos homozygous for this null allele hatch and, as larvae, c rawl, feed, and respond to stimuli. Electrophysiological recordings in embryonic cultures confirmed that synaptic transmission persists in t he null allele. Therefore, synaptotagmin is not absolutely required fo r the regulated exocytosis of synaptic vesicles. The lethality of syna ptotagmin in late first instar larvae is probably due to a perturbatio n of transmission that leaves the main apparatus for vesicle docking a nd fusion intact.