Septins are GTPases required for the completion of cytokinesis in diverse o
rganisms, yet their roles in cytokinesis or other cellular processes remain
unknown. Here we describe studies of a newly identified septin, CDCrel-1,
which is predominantly expressed in the nervous system. This protein was as
sociated with membrane fractions, and a significant fraction of the protein
copurified and coprecipitated with synaptic vesicles. In detergent extract
s, CDCrel-1 and another septin, Nedd5, immunoprecipitated with the SNARE pr
otein syntaxin by directly binding to syntaxin via the SNARE interaction do
main. Transfection of HIT-T15 cells with wild-type CDCrel-1 inhibited secre
tion, whereas GTPase dominant-negative mutants enhanced secretion. These da
ta suggest that septins may regulate vesicle dynamics through interactions
with syntaxin.