Rab3 dynamically controls protein composition at active zones.
Synaptic transmission requires the localization of presynaptic release machinery to active zones. Mechanisms regulating the abundance of such synaptic proteins at individual release sites are likely determinants of site-specific synaptic efficacy. We now identify a role for the small GTPase Rab3 in regulating the distribution of presynaptic components to active zones. At Drosophila rab3 mutant NMJs, the presynaptic protein Bruchpilot, calcium channels, and electron-dense T bars are concentrated at a fraction of available active zones, leaving the majority of sites devoid of these key presynaptic release components. Late addition of Rab3 to mutant NMJs rapidly reverses this phenotype by recruiting Brp to sites previously lacking the protein, demonstrating that Rab3 can dynamically control the composition of the presynaptic release machinery. While previous studies of Rab3 have focused on its role in the synaptic vesicle cycle, these findings demonstrate an additional and unexpected function for Rab3 in the localization of presynaptic proteins to active zones.
Graf
Ethan R
ER
Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Daniels
Richard W
RW
Burgess
Robert W
RW
Schwarz
Thomas L
TL
DiAntonio
Aaron
A
D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000494:pharmacology; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009045:Motor Endplate / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000166:cytology* / Q000187:drug effects; D017711:Nonlinear Dynamics; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D017470:Receptors, Glutamate / Q000235:genetics; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C510146:BRP protein, Drosophila; D029721:Drosophila Proteins; D017470:Receptors, Glutamate; C483908:glutamate receptor III, Drosophila; D049452:Green Fluorescent Proteins; D020692:rab3 GTP-Binding Proteins; D002118:Calcium