ArticleThe Journal of cell biology1994
Amino acid residues 24-31 but not palmitoylation of cysteines 30 and 45 are required for membrane anchoring of glutamic acid decarboxylase, GAD65.
Article in The Journal of cell biology, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 77 citations in OpenAlex.
- The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders.International journal of molecular sciences · 2025Review
- Regulation of Dynamic Protein S-Acylation.Frontiers in molecular biosciences · 2021Review
- Aberrant Accumulation of the Diabetes Autoantigen GAD65 in Golgi Membranes in Conditions of ER Stress and Autoimmunity.Diabetes · 2016Article
- Compartmentalization of GABA synthesis by GAD67 differs between pancreatic beta cells and neurons.PloS one · 2015Article
- Palmitoylation and trafficking of GAD65 are impaired in a cellular model of Huntington's disease.The Biochemical journal · 2012Article
- Calpain cleavage of brain glutamic acid decarboxylase 65 is pathological and impairs GABA neurotransmission.PloS one · 2012Article
- GABA(A) receptor and glycine receptor activation by paracrine/autocrine release of endogenous agonists: more than a simple communication pathway.Molecular neurobiology · 2011Review
- Two distinct mechanisms target GAD67 to vesicular pathways and presynaptic clusters.The Journal of cell biology · 2010Article
- Glutamate decarboxylase: loss of N-terminal segment does not affect homodimerization and determination of the oxidation state of cysteine residues.Neurochemical research · 2005Article
- Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase.The Journal of experimental medicine · 2003Article
- Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- A combination of three distinct trafficking signals mediates axonal targeting and presynaptic clustering of GAD65.The Journal of cell biology · 2002Article
- Localization of a peripheral membrane protein: Gbetagamma targets Galpha(Z).Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase and is required for synaptic transmission but not synaptic development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1999Article
- Plasma membrane localization is required for RGS4 function in Saccharomyces cerevisiae.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- The first 35 amino acids and fatty acylation sites determine the molecular targeting of endothelial nitric oxide synthase into the Golgi region of cells: a green fluorescent protein study.The Journal of cell biology · 1997Article
- Activity-independent segregation of excitatory and inhibitory synaptic terminals in cultured hippocampal neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1996Article
- Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus.The Journal of experimental medicine · 1994Article
- GAD, diabetes, and Stiff-Man syndrome: some progress and more questions.Journal of endocrinological investigationReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The smaller isoform of the GABA synthesizing enzyme glutamic acid decarboxylase, GAD65, is synthesized as a soluble protein that undergoes post-translational modification(s) in the NH2-terminal region to become anchored to the membrane of small synaptic-like microvesicles in pancreatic beta cells, and synaptic vesicles in GABA-ergic neurons. A soluble hydrophilic form, a soluble hydrophobic form, and a hydrophobic firmly membrane-anchored form have been detected in beta cells. A reversible and hydroxylamine sensitive palmitoylation has been shown to distinguish the firmly membrane-anchored form from the soluble yet hydrophobic form, suggesting that palmitoylation of cysteines in the NH2-terminal region is involved in membrane anchoring. In this study we use site-directed mutagenesis to identify the first two cysteines in the NH2-terminal region, Cys 30 and Cys 45, as the sites of palmitoylation of the GAD65 molecule. Mutation of Cys 30 and Cys 45 to Ala results in a loss of palmitoylation but does not significantly alter membrane association of GAD65 in COS-7 cells. Deletion of the first 23 amino acids at the NH2 terminus of the GAD65 30/45A mutant also does not affect the hydrophobicity and membrane anchoring of the GAD65 protein. However, deletion of an additional eight amino acids at the NH2 terminus results in a protein which is hydrophilic and cytosolic. The results suggest that amino acids 24-31 are required for hydrophobic modification and/or targeting of GAD65 to membrane compartments, whereas palmitoylation of Cys 30 and Cys 45 may rather serve to orient or fold the protein at synaptic vesicle membranes.
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