ArticlePloS one2015
Compartmentalization of GABA synthesis by GAD67 differs between pancreatic beta cells and neurons.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- A compact GAD67 promoter enables inhibitory neuron-targeted AAV gene therapy for seizure suppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Peripheral GABA Signaling in Metabolic Adaptation and Maladaptation.International journal of molecular sciences · 2026Review
- Molecular Basis of GABA Aminotransferase Inhibition in Epilepsy: Structure, Mechanisms, and Drug Development.Current issues in molecular biology · 2025Review
- The nerve center of organ engineering.Nature communications · 2025Review
- Neurotransmitter Alterations in Prediabetes and Type 2 Diabetes Mellitus: A Narrative Review.International journal of molecular sciences · 2025Review
- GABA and GLP-1 receptor agonist combination therapy modifies diabetes and Langerhans islet cytoarchitecture in a rat model of Wolfram syndrome.Diabetology & metabolic syndrome · 2025Article
- Review
- Assessment of neurotransmitter release in human iPSC-derived neuronal/glial cells: a missing in vitro assay for regulatory developmental neurotoxicity testing.Reproductive toxicology (Elmsford, N.Y.) · 2023Article
- Autoantibodies directed against glutamate decarboxylase interfere with glucose-stimulated insulin secretion in dispersed rat islets.International journal of experimental pathology · 2022Article
- A Novel ex vivo Method for Investigating Vascularization of Transplanted Islets.Journal of vascular research · 2022Article
- The role of GABA in islet function.Frontiers in endocrinology · 2022Review
- BDNF and JNK Signaling Modulate Cortical Interneuron and Perineuronal Net Development: Implications for Schizophrenia-Linked 16p11.2 Duplication Syndrome.Schizophrenia bulletin · 2021Article
- Prelimbic cortical targets of ventromedial thalamic projections include inhibitory interneurons and corticostriatal pyramidal neurons in the rat.Brain structure & function · 2020Article
- Prevention of Type 1 Diabetes: Past Experiences and Future Opportunities.Journal of clinical medicine · 2020Review
- Autoimmune encephalitis and epilepsy: evolving definition and clinical spectrum.Clinical and experimental pediatrics · 2020Article
- Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell.Nature metabolism · 2019Article
- Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets.Islets · 2019Article
- A novel homozygous mutation in GAD1 gene described in a schizophrenic patient impairs activity and dimerization of GAD67 enzyme.Scientific reports · 2018Article
- Functional Characterization of Native, High-Affinity GABAEBioMedicine · 2018Article
- GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4EBioMedicine · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The inhibitory neurotransmitter GABA is synthesized by the enzyme glutamic acid decarboxylase (GAD) in neurons and in pancreatic β-cells in islets of Langerhans where it functions as a paracrine and autocrine signaling molecule regulating the function of islet endocrine cells. The localization of the two non-allelic isoforms GAD65 and GAD67 to vesicular membranes is important for rapid delivery and accumulation of GABA for regulated secretion. While the membrane anchoring and trafficking of GAD65 are mediated by intrinsic hydrophobic modifications, GAD67 remains hydrophilic, and yet is targeted to vesicular membrane pathways and synaptic clusters in neurons by both a GAD65-dependent and a distinct GAD65-independent mechanism. Herein we have investigated the membrane association and targeting of GAD67 and GAD65 in monolayer cultures of primary rat, human, and mouse islets and in insulinoma cells. GAD65 is primarily detected in Golgi membranes and in peripheral vesicles distinct from insulin vesicles in β-cells. In the absence of GAD65, GAD67 is in contrast primarily cytosolic in β-cells; its co-expression with GAD65 is necessary for targeting to Golgi membranes and vesicular compartments. Thus, the GAD65-independent mechanism for targeting of GAD67 to synaptic vesicles in neurons is not functional in islet β-cells. Therefore, only GAD65:GAD65 homodimers and GAD67:GAD65 heterodimers, but not the GAD67:GAD67 homodimer gain access to vesicular compartments in β-cells to facilitate rapid accumulation of newly synthesized GABA for regulated secretion and fine tuning of GABA-signaling in islets of Langerhans.
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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.