ArticleThe Journal of cell biology2010
Two distinct mechanisms target GAD67 to vesicular pathways and presynaptic clusters.
Article in The Journal of cell biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
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- Long-Term Audiogenic Kindling Induces Pronounced Downregulation of the GABAergic System in the Hippocampus of Krushinsky-Molodkina Rats.The European journal of neuroscience · 2026Article
- Presynaptic Trafficking of Glutamate Decarboxylase Isoforms Is Dispensable for Basal GABAergic Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Context-tuned strategies for marker selection precision in neuronal studies.Frontiers in neuroscience · 2026Review
- Beta cell secreted GABA sets appropriate insulin secretion by modulating islet calcium oscillations.Molecular metabolism · 2025Article
- Downregulation of USP9X in the DG Region of the Hippocampus Leads to AD-Like Cognitive Dysfunction in Mice.CNS neuroscience & therapeutics · 2025Article
- Modulation of pain sensitivity by Ascl1- and Lhx6-dependent GABAergic neuronal function in streptozotocin diabetic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Schizophrenia-Like Deficits and Impaired Glutamate/Gamma-aminobutyric acid Homeostasis in Zfp804a Conditional Knockout Mice.Schizophrenia bulletin · 2024Article
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- Ivermectin modulated cerebral γ-aminobutyric acid (GABA) and reduced the number of chronicJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2023Article
- The GABA and GABA-Receptor System in Inflammation, Anti-Tumor Immune Responses, and COVID-19.Biomedicines · 2023Review
- Plexin-A1 expression in the inhibitory neurons of infralimbic cortex regulates the specificity of fear memory in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Cellular and molecular signatures of in vivo imaging measures of GABAergic neurotransmission in the human brain.Communications biology · 2022Article
- Leucine-Rich Repeats and Transmembrane Domain 2 Controls Protein Sorting in the Striatal Projection System and Its Deficiency Causes Disturbances in Motor Responses and Monoamine Dynamics.Frontiers in molecular neuroscience · 2022Article
- TNF-α Orchestrates Experience-Dependent Plasticity of Excitatory and Inhibitory Synapses in the Anterior Piriform Cortex.Frontiers in neuroscience · 2022Article
- Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery.Frontiers in cellular neuroscience · 2022Review
- Effect of Anti-inflammatory Treatment with AMD3100 and CXMolecular neurobiology · 2021Article
- Exercise Improved the Anti-Epileptic Effect of Carbamazepine through GABA Enhancement in Epileptic Rats.Neurochemical research · 2021Article
- Prelimbic cortical targets of ventromedial thalamic projections include inhibitory interneurons and corticostriatal pyramidal neurons in the rat.Brain structure & function · 2020Article
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
The inhibitory neurotransmitter gamma-amino butyric acid (GABA) is synthesized by two isoforms of the enzyme glutamic acid decarboxylase (GAD): GAD65 and GAD67. Whereas GAD67 is constitutively active and produces >90% of GABA in the central nervous system, GAD65 is transiently activated and augments GABA levels for rapid modulation of inhibitory neurotransmission. Hydrophobic lipid modifications of the GAD65 protein target it to Golgi membranes and synaptic vesicles in neuroendocrine cells. In contrast, the GAD67 protein remains hydrophilic but has been shown to acquire membrane association by heterodimerization with GAD65. Here, we identify a second mechanism that mediates robust membrane anchoring, axonal targeting, and presynaptic clustering of GAD67 but that is independent of GAD65. This mechanism is abolished by a leucine-103 to proline mutation that changes the conformation of the N-terminal domain but does not affect the GAD65-dependent membrane anchoring of GAD67. Thus two distinct mechanisms target the constitutively active GAD67 to presynaptic clusters to facilitate accumulation of GABA for rapid delivery into synapses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.