aex-3 encodes a novel regulator of presynaptic activity in C. elegans.
C. elegans aex-3 mutations cause pleiotropic behavioral defects that are suggestive of reduced synaptic transmission. aex-3 mutations also show strong genetic interactions with mutations in unc-31 and unc-64, two other genes implicated in synaptic transmission. Physiological and pharmacological studies indicate that aex-3 defects are presynaptic. In aex-3 mutants, the synaptic vesicle-associated RAB-3 protein aberrantly accumulates in neuronal cell bodies and is reduced in synapse-rich axons. This localization defect is specific to RAB-3, since other synaptic proteins are localized normally in aex-3 mutants. aex-3 encodes a 1409 amino acid protein with strong homology to DENN, a human protein of unknown function. In C. elegans, aex-3 is expressed in all or nearly all neurons. These results suggest that AEX-3 is a novel regulator of presynaptic activity that interacts with RAB-3 to regulate synaptic vesicle release.
Iwasaki
K
K
Department of Genetics, University of Washington, Seattle 98195, USA.
Staunton
J
J
Saifee
O
O
Nonet
M
M
Thomas
J H
JH
D000448:Aldicarb / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002874:Chromosome Mapping; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005796:Genes; D008969:Molecular Sequence Data; D009154:Mutation; D009424:Nervous System Physiological Phenomena; D010614:Pharynx / Q000294:innervation; D017729:Presynaptic Terminals / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission; D014018:Tissue Distribution; D020692:rab3 GTP-Binding Proteins
D002800:Cholinesterase Inhibitors; D000448:Aldicarb; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins