title: Caenorhabditis elegans rab-3 mutant synapses exhibit impaired function and are partially depleted of vesicles.
abstract: Rab molecules regulate vesicular trafficking in many different exocytic and endocytic transport pathways in eukaryotic cells. In neurons, rab3 has been proposed to play a crucial role in regulating synaptic vesicle release. To elucidate the role of rab3 in synaptic transmission, we isolated and characterized Caenorhabditis elegans rab-3 mutants. Similar to the mouse rab3A mutants, these mutants survived and exhibited only mild behavioral abnormalities. In contrast to the mouse mutants, synaptic transmission was perturbed in these animals. Extracellular electrophysiological recordings revealed that synaptic transmission in the pharyngeal nervous system was impaired. Furthermore, rab-3 animals were resistant to the acetylcholinesterase inhibitor aldicarb, suggesting that cholinergic transmission was generally depressed. Last, synaptic vesicle populations were redistributed in rab-3 mutants. In motor neurons, vesicle populations at synapses were depleted to 40% of normal levels, whereas in intersynaptic regions of the axon, vesicle populations were elevated. On the basis of the morphological defects at neuromuscular junctions, we postulate that RAB-3 may regulate recruitment of vesicles to the active zone or sequestration of vesicles near release sites.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Nonet
authors.forename: J E
authors.initials: JE
authors.lastname: Staunton
authors.forename: M P
authors.initials: MP
authors.lastname: Kilgard
authors.forename: T
authors.initials: T
authors.lastname: Fergestad
authors.forename: E
authors.initials: E
authors.lastname: Hartwieg
authors.forename: H R
authors.initials: HR
authors.lastname: Horvitz
authors.forename: E M
authors.initials: EM
authors.lastname: Jorgensen
authors.forename: B J
authors.initials: BJ
authors.lastname: Meyer
mesh_terms: D000448:Aldicarb / Q000633:toxicity; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D002417:Cattle; D002633:Chemotaxis; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003001:Cloning, Molecular; D004331:Drosophila melanogaster / Q000737:chemistry; D005089:Exocytosis / Q000235:genetics; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000648:ultrastructure; D010243:Paralysis / Q000139:chemically induced; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013569:Synapses / Q000737:chemistry / Q000648:ultrastructure*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D013572:Synaptic Vesicles / Q000473:pathology*; D020692:rab3 GTP-Binding Proteins
chemical_list: D002800:Cholinesterase Inhibitors; D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; D000448:Aldicarb; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins