ArticleCell reports2021
Huntingtin-mediated axonal transport requires arginine methylation by PRMT6.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Hyperglycemic stress aggravates diabetic retinopathy and nephropathy by promoting cilium disassembly via a deacetylation- and methylation-mediated regulatory mechanism.PLoS biology · 2026Article
- Mutant Huntingtin disrupts neurogenic and astroglial programs via the EZH2-Let-7g-LIN28 axis with rescue by epigenetic modulators.Cell death and differentiation · 2026Article
- PRMT6-mediated EZH2 arginine methylation is critical for breast cancer development.Oncogenesis · 2026Article
- Huntingtin and its allies at the cortico-striatal synapse.Cell death & disease · 2026Review
- High Content In Vitro Survival Assay of Cortical Neurons.Bio-protocol · 2026Article
- Protein Arginine Methyltransferases from Regulatory Function to Clinical Implication in Central Nervous System.Cellular and molecular neurobiology · 2025Review
- Therapeutic approaches targeting aging and cellular senescence in Huntington's disease.CNS neuroscience & therapeutics · 2024Review
- Peripheral sequestration of huntingtin delays neuronal death and depends on N-terminal ubiquitination.Communications biology · 2024Article
- Sequencing-guided design of genetically encoded small RNAs targeting CAG repeats for selective inhibition of mutantMolecular therapy. Nucleic acids · 2024Article
- Neuropathogenesis-on-chips for neurodegenerative diseases.Nature communications · 2024Review
- Protective Proteolysis in Huntington's Disease: Unraveling the Role of Post-Translational Myristoylation of Huntingtin in Autophagy.Journal of Huntington's disease · 2024Review
- Arginine methylation of RNA-binding proteins is impaired in Huntington's disease.Human molecular genetics · 2023Article
- Critical Roles of Protein Arginine Methylation in the Central Nervous System.Molecular neurobiology · 2023Review
- Functional Implications of Protein Arginine Methyltransferases (PRMTs) in Neurodegenerative Diseases.Biology · 2023Review
- Article
- Disruption of axonal transport in neurodegeneration.The Journal of clinical investigation · 2023Review
- LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice.Nature communications · 2023Article
- Review
- Protein Kinase CK2 and Its Potential Role as a Therapeutic Target in Huntington's Disease.Biomedicines · 2022Review
- Molecular Pathophysiological Mechanisms in Huntington's Disease.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
18 authors at 9 institutions in 4 countries.
Funding
Abstract
The huntingtin (HTT) protein transports various organelles, including vesicles containing neurotrophic factors, from embryonic development throughout life. To better understand how HTT mediates axonal transport and why this function is disrupted in Huntington's disease (HD), we study vesicle-associated HTT and find that it is dimethylated at a highly conserved arginine residue (R118) by the protein arginine methyltransferase 6 (PRMT6). Without R118 methylation, HTT associates less with vesicles, anterograde trafficking is diminished, and neuronal death ensues-very similar to what occurs in HD. Inhibiting PRMT6 in HD cells and neurons exacerbates mutant HTT (mHTT) toxicity and impairs axonal trafficking, whereas overexpressing PRMT6 restores axonal transport and neuronal viability, except in the presence of a methylation-defective variant of mHTT. In HD flies, overexpressing PRMT6 rescues axonal defects and eclosion. Arginine methylation thus regulates HTT-mediated vesicular transport along the axon, and increasing HTT methylation could be of therapeutic interest for HD.
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Registered trials
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.