Ca2+/calmodulin causes Rab3A to dissociate from synaptic membranes.
The GTPase Rab3A has been postulated to cycle on and off synaptic membranes during the course of neurotransmission. Moreover, a Rab guanine nucleotide dissociation inhibitor has been shown to cause Rab3A to dissociate from synaptic membranes in vitro. We demonstrate here that Ca2+/calmodulin also can cause Rab3A to dissociate from synaptic membranes in vitro. Like Rab guanine nucleotide dissociation inhibitor, it forms a 1:1 complex with Rab3A that requires both the lipidated C terminus of Rab3A and the presence of bound guanine nucleotide. In addition, a synthetic peptide corresponding to the Lys62-Arg85 sequence of Rab3A can prevent the dissociating effect of each protein and disrupt complexes between each protein and Rab3A. However, Ca2+/calmodulin's effect differs from that of Rab guanine nucleotide dissociation inhibitor not only in being Ca2+-dependent but also in having a less stringent requirement for GDP as opposed to GTP and in involving a less complete dissociation of Rab3A. The functional significance in vivo of Ca2+/calmodulin's effect remains to be determined; it may depend in part on the relative amounts of Ca2+/calmodulin and Rab guanine nucleotide dissociation inhibitor that are available for binding to Rab3A in individual, activated nerve termini.
Park
J B
JB
Howard Hughes Medical Institute, Department of Medicine, University of Washington, Seattle, Washington 98195-7370, USA.
Farnsworth
C C
CC
Glomset
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D008970:Molecular Weight; D013570:Synaptic Membranes / Q000378:metabolism*; D020692:rab3 GTP-Binding Proteins
D002147:Calmodulin; C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; D002118:Calcium