TY - JOUR T1 - A Product of the <em>Drosophila stoned </em>Locus Regulates Neurotransmitter Release JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9638 LP - 9649 DO - 10.1523/JNEUROSCI.18-23-09638.1998 VL - 18 IS - 23 AU - Daniel T. Stimson AU - Patricia S. Estes AU - Michiko Smith AU - Leonard E. Kelly AU - Mani Ramaswami Y1 - 1998/12/01 UR - http://www.jneurosci.org/content/18/23/9638.abstract N2 - The Drosophila stoned locus encodes two novel gene products termed stonedA and stonedB, which possess sequence motifs shared by proteins involved in intracellular vesicle traffic. A specific requirement for stoned in the synaptic vesicle cycle has been suggested by synthetic genetic interactions betweenstoned and shibire, a gene essential for synaptic vesicle recycling (Petrovich et al., 1993). A synaptic role ofstoned gene products also is suggested by altered synaptic transients in electroretinograms recorded from stonedmutant eyes (Petrovich et al., 1993). We show here that the stonedA protein is highly enriched at Drosophila nerve terminals. Mutant alleles that affect stonedA disrupt the normal regulation of synaptic vesicle exocytosis at neuromuscular synapses ofDrosophila. Spontaneous neurotransmitter release is enhanced dramatically, and evoked release is reduced substantially in such stoned mutants. Ultrastructural studies reveal no evidence of major disorganization at stonedmutant nerve terminals. Thus, our data indicate a direct role for stonedA in regulating synaptic vesicle exocytosis. However, genetic and morphological observations suggest additional, subtle effects ofstoned mutations on synaptic vesicle recycling. Remarkably, almost all phenotypes of stoned mutants are similar to those previously described for mutants of synaptotagmin, a protein postulated to regulate both exocytosis and the recycling of synaptic vesicles. We propose a model in which stonedA functions together with synaptotagmin to regulate synaptic vesicle cycling. ER -