ArticleThe Journal of cell biology2022
Impaired XK recycling for importing manganese underlies striatal vulnerability in Huntington's disease.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 10 citations in OpenAlex.
- Neuropathological Characterisation of McLeod Syndrome With a Proposed New Grading System.Neuropathology and applied neurobiology · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Chronic pharmacologic manipulation of dopamine transmission ameliorates metabolic disturbance in Trappc9-linked brain developmental syndrome.JCI insight · 2024Article
- Proteotoxic stresses stimulate dissociation of UBL4A from the tail-anchored protein recognition complex.The Biochemical journal · 2023Article
- The role of the symbiotic microecosystem in cancer: gut microbiota, metabolome, and host immunome.Frontiers in immunology · 2023Review
- A novel necroptosis-related long noncoding RNA model for predicting clinical features, immune characteristics, and therapeutic response in clear cell renal cell carcinoma.Frontiers in immunology · 2023Article
- Endosomal recycling defects link Huntington's disease with McLeod syndrome.The Journal of cell biology · 2022Article
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13 authors at 3 institutions in 3 countries.
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Abstract
Mutant huntingtin, which causes Huntington's disease (HD), is ubiquitously expressed but induces preferential loss of striatal neurons by unclear mechanisms. Rab11 dysfunction mediates homeostatic disturbance of HD neurons. Here, we report that Rab11 dysfunction also underscores the striatal vulnerability in HD. We profiled the proteome of Rab11-positive endosomes of HD-vulnerable striatal cells to look for protein(s) linking Rab11 dysfunction to striatal vulnerability in HD and found XK, which triggers the selective death of striatal neurons in McLeod syndrome. XK was trafficked together with Rab11 and was diminished on the surface of immortalized HD striatal cells and striatal neurons in HD mouse brains. We found that XK participated in transporting manganese, an essential trace metal depleted in HD brains. Introducing dominantly active Rab11 into HD striatal cells improved XK dynamics and increased manganese accumulation in an XK-dependent manner. Our study suggests that impaired Rab11-based recycling of XK onto cell surfaces for importing manganese is a driver of striatal dysfunction in Huntington's disease.
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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.