title: Rab3-GAP controls the progression of synaptic homeostasis at a late stage of vesicle release.
abstract: Homeostatic signaling systems stabilize neural function through the modulation of neurotransmitter receptor abundance, ion channel density, and presynaptic neurotransmitter release. Molecular mechanisms that drive these changes are being unveiled. In theory, molecular mechanisms may also exist to oppose the induction or expression of homeostatic plasticity, but these mechanisms have yet to be explored. In an ongoing electrophysiology-based genetic screen, we have tested 162 new mutations for genes involved in homeostatic signaling at the Drosophila NMJ. This screen identified a mutation in the rab3-GAP gene. We show that Rab3-GAP is necessary for the induction and expression of synaptic homeostasis. We then provide evidence that Rab3-GAP relieves an opposing influence on homeostasis that is catalyzed by Rab3 and which is independent of any change in NMJ anatomy. These data define roles for Rab3-GAP and Rab3 in synaptic homeostasis and uncover a mechanism, acting at a late stage of vesicle release, that opposes the progression of homeostatic plasticity.
authors.affiliation: Department of Biochemistry and Biophysics, 1550 4th Street, Rock Hall 4th Floor North, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.forename: Edward C G
authors.initials: EC
authors.lastname: Pym
authors.forename: Amy
authors.initials: A
authors.lastname: Tong
authors.forename: Graeme W
authors.initials: GW
authors.lastname: Davis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011073:Polyamines / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism*; D050857:Synaptotagmins / Q000378:metabolism; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D018733:Nicotinic Antagonists; D011073:Polyamines; D017470:Receptors, Glutamate; D050857:Synaptotagmins; D049452:Green Fluorescent Proteins; C034092:delta-philanthotoxin; D020692:rab3 GTP-Binding Proteins; D002118:Calcium