Genetic modifiers of the Drosophila NSF mutant, comatose, include a temperature-sensitive paralytic allele of the calcium channel alpha 1-subunit gene, cacophony

The N-ethylmaleimide-sensitive fusion protein (NSF) has been implicated in vesicle trafficking in perhaps all eukaryotic cells. The Drosophila comatos e (comt) gene encodes an NSF homolog, dNSF1. Our previous work with tempera ture-sensitive (TS) paralytic alleles of comt has revealed a function for d NSF1 at synapses, where it appears to prime synaptic vesicles for neurotran smitter release. To further examine the molecular basis of dNSF1 function a nd to broaden our analysis of synaptic transmission to other gene products, we have performed a genetic screen for mutations that interact with comt. Here we report the isolation and analysis of four mutations that modify TS paralysis in comt, including two intragenic modifiers tone enhancer and one suppressor) and two extragenic modifiers (both enhancers). The intragenic mutations will contribute to structure-function analysis of dNSF1 and the e xtragenic mutations identify gene products with related functions in synapt ic transmission. Both extragenic enhancers result in TS behavioral phenotyp es when separated from comt, and both map to loci not previously identified in screens for TS mutants. One of these mutations is a TS paralytic allele of the calcium channel alpha 1-subunit gene, cacophony (cac). Analysis of synaptic function in these mutants alone and in combination will further de fine the in vivo functions and interactions of specific gene products in sy naptic transmission.