ArticleThe Biochemical journal2012
Palmitoylation and trafficking of GAD65 are impaired in a cellular model of Huntington's disease.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Influence of palmitoylation in axonal transport mechanisms in neurodegenerative diseases.Frontiers in cellular neuroscience · 2025Review
- Characterization of huntingtin interactomes and their dynamic responses in living cells by proximity proteomics.Journal of neurochemistry · 2023Article
- ABHD6 Inhibition Rescues a Sex-Dependent Deficit in Motor Coordination in The HdhQ200/200 Mouse Model of Huntington's Disease.Journal of neurology and neurological disorders · 2021Article
- Acute Regulation of Habituation Learning via Posttranslational Palmitoylation.Current biology : CB · 2020Article
- Article
- Spatial organization of palmitoyl acyl transferases governs substrate localization and function.Molecular membrane biology · 2019Review
- EGF Treatment Improves Motor Behavior and Cortical GABAergic Function in the R6/2 Mouse Model of Huntington's Disease.Molecular neurobiology · 2019Article
- Altered Regulation of Striatal NeuronalFrontiers in synaptic neuroscience · 2019Article
- Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies.Chemical reviews · 2018Article
- A systematic analysis of protein palmitoylation in Caenorhabditis elegans.BMC genomics · 2014Article
- The palmitoyl acyltransferase HIP14 shares a high proportion of interactors with huntingtin: implications for a role in the pathogenesis of Huntington's disease.Human molecular genetics · 2014Article
- S-palmitoylation regulates biogenesis of core glycosylated wild-type and F508del CFTR in a post-ER compartment.The Biochemical journal · 2014Article
- Altered Neuronal Dynamics in the Striatum on the Behavior of Huntingtin Interacting Protein 14 (HIP14) Knockout Mice.Brain sciences · 2013Article
- Dysregulated striatal neuronal processing and impaired motor behavior in mice lacking huntingtin interacting protein 14 (HIP14).PloS one · 2013Article
- Amino-terminal cysteine residues differentially influence RGS4 protein plasma membrane targeting, intracellular trafficking, and function.The Journal of biological chemistry · 2012Article
- Metallo-β-lactamase domain-containing protein 2 is S-palmitoylated and exhibits acyl-CoA hydrolase activity.The Journal of biological chemistryArticle
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5 authors at 1 institution in 1 country.
Funding
Abstract
HD (Huntington's disease) is caused by an expanded polyQ (polyglutamine) repeat in the htt (huntingtin protein). GABAergic medium spiny neurons in the striatum are mostly affected in HD. However, mhtt (mutant huntingtin)-induced molecular changes in these neurons remain largely unknown. The present study focuses on the effect of mhtt on the subcellular localization of GAD (glutamic acid decarboxylase), the enzyme responsible for synthesizing GABA (γ-aminobutyric acid). We report that the subcellular distribution of GAD is significantly altered in two neuronal cell lines that express either the N-terminus of mhtt or full-length mhtt. GAD65 is predominantly associated with the Golgi membrane in cells expressing normal htt; however, it diffuses in the cytosol of cells expressing mhtt. As a result, vesicle-associated GAD65 trafficking is impaired. Since palmitoylation of GAD65 is required for GAD65 trafficking, we then demonstrate that palmitoylation of GAD65 is reduced in the HD model. Furthermore, overexpression of HIP14 (huntingtin-interacting protein 14), the enzyme responsible for palmitoylating GAD65 in vivo, could rescue GAD65 palmitoylation and vesicle-associated GAD65 trafficking. Taken together, our data support the idea that GAD65 palmitoylation is important for the delivery of GAD65 to inhibitory synapses and suggest that impairment of GAD65 palmitoylation by mhtt may lead to altered inhibitory neurotransmission in HD.
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