CA2+ CALMODULIN CAUSES RAB3A TO DISSOCIATE FROM SYNAPTIC-MEMBRANES/

The GTPase Rab3A has been postulated to cycle on and off synaptic memb ranes during the course of neurotransmission. Moreover, a Rab guanine nucleotide dissociation inhibitor has been shown to cause Rab3A to dis sociate from synaptic membranes in vitro, Pie demonstrate here that Ca 2+/calmodulin also can cause Rab3A to dissociate from synaptic membran es in vitro. Like Rab guanine nucleotide dissociation inhibitor, it fo rms a 1:1 complex with Rab3A that requires both the lipidated C termin us of Rab3A and the presence of bound guanine nucleotide. In addition, a synthetic peptide corresponding to the Lys(62)-Arg(85) sequence of Rab3A can prevent the dissociating effect of each protein and disrupt complexes between each protein and Rab3A. However, Ca2+/calmodulin's e ffect differs from that of Rab guanine nucleotide dissociation inhibit or not only in being Ca2+-dependent but also in having a less stringen t requirement for GDP as opposed to GTP and in involving a less comple te dissociation of Rab3A The functional significance in vivo of Ca2+/c almodulin's effect remains to be determined; it may depend in part on the relative amounts of Ca2+/calmodulin and Rab guanine nucleotide dis sociation inhibitor that are available for binding to Rab3A in individ ual, activated nerve termini.