Direct interaction between the ARF-specific guanine nucleotide exchange factor msec7-1 and presynaptic Munc13-1

Msec7-1, a mammalian homologue of yeast sec7p, is a specific GDP/GTP exchan ge factor for small G-proteins of the ARF family. Overexpression of msec7-1 in Xenopus neuromuscular junctions leads to an increase in synaptic transm itter release that is most likely caused by an increase in the pool of read ily releasable vesicles. However, the molecular mechanisms by which msec7-1 is targeted to presynaptic compartments and enhances neurotransmitter rele ase are not known. In the present study, we demonstrate that msec7-1 intera cts directly with Munc13-1, a phorbol ester-dependent enhancer of neurotran smitter release that is specifically localized to presynaptic transmitter r elease zones. Given that Munc13-1 and msec7-1 participate in very similar p resynaptic processes and because Munc13-1 is specifically targeted to presy naptic active zones, we suggest that the msec7-1/Munc13-1 interaction serve s to colocalize the two proteins at the active zone, a subcellular compartm ent with extremely high membrane turnover.