The Caenorhabditis elegans Gene unc-25Encodes 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 theCaenorhabditis elegans gene unc-25encodes 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.

• Publication year

  1999

• Venue

  Journal of Neuroscience

• Publication date

  1999-01-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.19-02-00539.1999PMID 9880574PMCID PMC6782196
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Differential localization of two glutamic acid decarboxylases (GAD65 and GAD67) in adult monkey visual cortex

  2004cited by this paper
• Molecular Cloning: A Laboratory Manual

  2001cited by this paper
• Synaptic Transmission Deficits in Caenorhabditis elegansSynaptobrevin Mutants

  1998cited by this paper
• Intron-mediated enhancement of transgene expression in maize is a nuclear, gene-dependent process.

  1997cited by this paper
• Cleft palate in mice with a targeted mutation in the gamma-aminobutyric acid-producing enzyme glutamic acid decarboxylase 67.

  1997cited by this paper
• Phosphorylation of Serine Residues 3, 6, 10, and 13 Distinguishes Membrane Anchored from Soluble Glutamic Acid Decarboxylase 65 and Is Restricted to Glutamic Acid Decarboxylase 65α*

  1997cited by this paper
• Translational attenuation mediated by an mRNA intron.

  1997cited by this paper
• Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase.

  1997cited by this paper
• Calcium and chemotropic turning of nerve growth cones.

  1996cited by this paper
• GABA and GABA-A receptors are maximally expressed in association with cone synaptogenesis in neonatal rabbit retina.

  1996cited by this paper
• Essential role of filopodia in chemotropic turning of nerve growth cone induced by a glutamate gradient

  1996cited by this paper
• A sperm-supplied factor required for embryogenesis in C. elegans.

  1996cited by this paper
• Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures.

  1996cited by this paper
• Dual function of the intron of the rat insulin I gene in regulation of gene expression

  1996cited by this paper
• GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis.

  1995influential reference
• Reversal of a muscle response to GABA during C. elegans male development

  1995cited by this paper
• Defective recycling of synaptic vesicles in synaptotagmin mutants of Caenorhabditis elegans

  1995cited by this paper
• Caenorhabditis elegans : modern biological analysis of an organism

  1995cited by this paper
• GABA‐induced motility of spinal neuroblasts develops along a ventrodorsal gradient and can be mimicked by agonists of GABAA and GABAB receptors

  1995cited by this paper
• ACeDB and macace.

  1995cited by this paper
• Amino acid residues 24-31 but not palmitoylation of cysteines 30 and 45 are required for membrane anchoring of glutamic acid decarboxylase, GAD65

  1994cited by this paper
• The Regulation of Gene Expression in Transformed Maize Aleurone and Endosperm Protoplasts (Analysis of Promoter Activity, Intron Enhancement, and mRNA Untranslated Regions on Expression)

  1994cited by this paper
• Induction of human interleukin-1 gene expression by retinoic acid and its regulation at processing of precursor transcripts.

  1994cited by this paper
• A signal located within amino acids 1-27 of GAD65 is required for its targeting to the Golgi complex region

  1994cited by this paper
• Turning of nerve growth cones induced by neurotransmitters

  1994cited by this paper
• Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms

  1994cited by this paper
• The Caenorhabditis elegans NK-2 class homeoprotein CEH-22 is involved in combinatorial activation of gene expression in pharyngeal muscle.

  1994cited by this paper
• Posttranscriptional regulation of thymidylate synthase gene expression

  1994cited by this paper
• Green fluorescent protein as a marker for gene expression.

  1994influential reference
• Drosophila GABAergic systems II. Mutational analysis of chromosomal segment 64AB, a region containing the glutamic acid decarboxylase gene

  1994cited by this paper
• The exon-intron organization of the genes (GAD1 and GAD2) encoding two human glutamate decarboxylases (GAD67 and GAD65) suggests that they derive from a common ancestral GAD.

  1994influential reference
• Localization of mRNAs encoding two forms of glutamic acid decarboxylase in the rat hippocampal formation

  1994cited by this paper
• The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins.

  1994cited by this paper
• The role of GABA during development of the outer retina in the rabbit

  1993cited by this paper
• Genes required for GABA function in Caenorhabditis elegans

  1993influential reference
• The GABAergic nervous system of Caenorhabditis elegans

  1993influential reference
• Regulation of γ‐Aminobutyric Acid Synthesis in the Brain

  1993cited by this paper
• Regulation of gamma-aminobutyric acid synthesis in the brain.

  1993cited by this paper
• A Neural Gene from Drosophila melanogaster with Homology to Vertebrate and Invertebrate Glutamate Decarboxylases

  1993cited by this paper
• Genes necessary for directed axonal elongation or fasciculation in C. elegans.

  1992cited by this paper
• A survey of expressed genes in Caenorhabditis elegans

  1992cited by this paper
• Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans.

  1991influential reference
• The C. elegans unc-104 gene encodes a putative kinesin heavy chain-like protein.

  1991cited by this paper
• Two genes encode distinct glutamate decarboxylases.

  1991cited by this paper
• Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences.

  1991cited by this paper
• The structural and functional heterogeneity of glutamic acid decarboxylase: A review

  1991cited by this paper
• The regulation of synaptogenesis during normal development and following activity blockade

  1991cited by this paper
• Pathfinding and synapse formation in a zebrafish mutant lacking functional acetylcholine receptors.

  1990cited by this paper
• A modular set of lacZ fusion vectors for studying gene expression in Caenorhabditis elegans.

  1990cited by this paper
• The Caenorhabditis elegans rol-6 gene, which interacts with the sqt-1 collagen gene to determine organismal morphology, encodes a collagen

  1990cited by this paper
• Drosophila GABAergic Systems: Sequence and Expression of Glutamic Acid Decarboxylase

  1990cited by this paper
• Molecular cloning : a laboratory manual. Cold Spring Harbor, NY

  1989cited by this paper
• The earliest-generated neurons of the cat cerebral cortex: characterization by MAP2 and neurotransmitter immunohistochemistry during fetal life

  1989cited by this paper
• Neurotransmitter regulation of neuronal outgrowth, plasticity and survival.

  1989cited by this paper
• The basal component of the nematode dense-body is vinculin.

  1989cited by this paper
• [Genetics of Caenorhabditis elegans].

  1989influential reference
• Neurotransmitters in the regulation of neuronal cytoarchitecture.

  1988cited by this paper
• Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons

  1988cited by this paper
• The structure of the nervous system of the nematode Caenorhabditis elegans.

  1986cited by this paper
• Male Phenotypes and Mating Efficiency in CAENORHABDITIS ELEGANS.

  1983cited by this paper
• Pathway selection by embryonic chick motoneurons in an experimentally altered environment

  1981cited by this paper
• The genetics of Caenorhabditis elegans.

  1974cited by this paper

• Serotonergic Signaling Governs Caenorhabditis elegans Sensory Response to Conflicting Chemosensory Stimuli

  2025cites this paper
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  2025cites this paper
• Exposure to Benzotriazole UV Stabilizer-329 at Environmental Concentrations Induces Neurotoxicity by Affecting Neurotransmission in Caenorhabditis elegans.

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• C. elegans as a powerful model for neurotoxicity assessment.

  2025cites this paper
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  2025cites this paper
• Short- and long-range roles of UNC-6/Netrin in dorsal-ventral axon guidance in vivo in Caenorhabditis elegans

  2025cites this paper
• Sensory plasticity caused by up-down regulation encodes the information of short-term learning and memory

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• Serotonergic signaling governs C. elegans sensory response to conflicting olfactory stimuli

  2025cites this paper
• Neuro-intestinal acetylcholine signalling regulates the mitochondrial stress response in Caenorhabditis elegans

  2024cites this paper
• A leak K+ channel TWK-40 sustains the rhythmic motor program

  2024cites this paper
• Distinct mechanisms of non-autonomous UPRER mediated by GABAergic, glutamatergic, and octopaminergic neurons

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• Differential roles of lysosomal cholesterol transporters in the development of C. elegans NMJs

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  2024cites this paper
• β-asarone Protects Against Age-related Motor Decline via Activation of SKN-1/Nrf2 and Subsequent Induction of GST-4.

  2024cites this paper
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• A neurotransmitter atlas of C. elegans males and hermaphrodites

  2024cites this paper
• Glial KCNQ K+ channels control neuronal output by regulating GABA release from glia in C. elegans.

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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
• Toxicity Assessment of Urban Dust from Barranquilla, a Colombian Caribbean City, using Caenorhabditis elegans

  2023influential citation
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  2023cites this paper
• Femtosecond laser microdissection for isolation of regenerating C. elegans neurons for single-cell RNA sequencing

  2023cites this paper
• Synaptogenesis: unmasking molecular mechanisms using Caenorhabditis elegans.

  2023cites this paper
• An ancient thyrostimulin-like neuroendocrine pathway regulates growth in Caenorhabditis elegans

  2023cites this paper
• UBR‐1 ubiquitin ligase regulates the balance between GABAergic and glutamatergic signaling

  2023cites this paper
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  2023cites this paper
• GABAergic signaling between enteric neurons and intestinal smooth muscle promotes innate immunity and gut defense in Caenorhabditis elegans.

  2023cites this paper
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  2023cites this paper
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  2023influential citation
• Photoaged microplastics induce neurotoxicity associated with damage to serotonergic, glutamatergic, dopaminergic, and GABAergic neuronal systems in Caenorhabditis elegans.

  2023cites this paper
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  2022cites this paper
• Gut neuroendocrine signaling regulates synaptic assembly in C. elegans

  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2021cites this paper
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  2020cites this paper
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  2020influential citation
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  2020cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019influential citation
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
• Worminator: A platform to enable bio-inspired (C. elegans) robotics

  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018influential citation
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  2018cites this paper
• Surface Chemical Modification to Reduce the Toxicity of Nanomaterials

  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2017influential citation
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2016cites this paper