A presynaptic role for the ADP ribosylation factor (ARF)-specific GDP/GTP exchange factor msec7-1

ADP ribosylation factors (ARFs) represent a family of small monomeric G pro teins that switch from an inactive, GDP-bound state to an active, GTP-bound state. One member of this family, ARF6, translocates on activation from in tracellular compartments to the plasma membrane and has been implicated in regulated exocytosis in neuroendocrine cells. Because GDP release in vivo i s rather slow: ARF activation is facilitated by specific guanine nucleotide exchange factors like cytohesin-1 or ARNO, Here we show that msec7-1, a ra t homologue of cytohesin-1, translocates ARF6 to the plasma membrane in liv ing cells, Overexpression of msec7-1 leads to an increase in basal synaptic transmission at the Xenopus neuromuscular junction. msec7-1-containing syn apses have a 5-fold higher frequency of spontaneous synaptic currents than control synapses. On stimulation, the amplitudes of the resulting evoked po stsynaptic currents of msec7-1-overexpressing neurons are increased as well . However, further stimulation leads to a decline in amplitudes approaching the values of control synapses, This transient effect on amplitude is stro ngly reduced on overexpression of msec71E157K, a mutant incapable of transl ocating ARFs, Our results provide evidence that small G proteins of the ARF family and activating factors like msec7-1 play an important role in synap tic transmission, most likely by making more vesicles available for fusion at the plasma membrane.