The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase and is required for synaptic transmission but not synaptic development.
The neurotransmitter GABA has been proposed to play a role during nervous system development. We show that the Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase (GAD), the GABA biosynthetic enzyme. unc-25 is expressed specifically in GABAergic neurons. Null mutations in unc-25 eliminate the UNC-25 protein or alter amino acids conserved in all known GADs, result in a complete lack of GABA, and cause defects in all GABA-mediated behaviors. In unc-25 mutants the GABAergic neurons have normal axonal trajectories and synaptic connectivity, and the size and shape of synaptic vesicles are normal. The number of synaptic vesicles at GABAergic neuromuscular junctions is slightly increased. Cholinergic ventral nerve cord neurons, which innervate the same muscles as GABAergic ventral cord neurons, have normal morphology, connectivity, and synaptic vesicles. We conclude that GAD activity and GABA are not necessary for the development or maintenance of neuromuscular junctions in C. elegans.
Jin
Y
Y
Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz, California 95064, USA.
Jorgensen
E
E
Hartwieg
E
E
Horvitz
H R
HR
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009469:Neuromuscular Junction / Q000201:enzymology / Q000502:physiology; D010641:Phenotype; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase