ArticleHuman molecular genetics2017
Amino acid substitution equivalent to human chorea-acanthocytosis I2771R in yeast Vps13 protein affects its binding to phosphatidylinositol 3-phosphate.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Four subtypes of disease-causing missense mutations underlie pathogenic protein interactions in neurodegenerative VPS13A disease.The Journal of clinical investigation · 2026Article
- Proceedings of the 12Tremor and other hyperkinetic movements (New York, N.Y.) · 2026Article
- A novel VPS13A mutation in an Iranian family with Chorea-Acanthocytosis.Neurogenetics · 2025Article
- VPS13 and bridge-like lipid transporters, mechanisms, and mysteries.Frontiers in neuroscience · 2025Review
- Physiological and Pathogenesis Significance of Chorein in Health and Disease.Physiological research · 2024Review
- A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting.The Journal of cell biology · 2024Article
- Exploring the pathophysiological mechanisms and wet biomarkers ofFrontiers in neurology · 2024Review
- Parallel phospholipid transfer by Vps13 and Atg2 determines autophagosome biogenesis dynamics.The Journal of cell biology · 2023Article
- The association of lipid transfer protein VPS13A with endosomes is mediated by sorting nexin SNX5.Life science alliance · 2023Article
- A novel superfamily of bridge-like lipid transfer proteins.Trends in cell biology · 2022Review
- Validation of the Pathogenic Effect ofInternational journal of molecular sciences · 2022Article
- A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at the plasma membrane.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome.Scientific reports · 2022Article
- Yeast as a Model to Find New Drugs and Drug Targets forInternational journal of molecular sciences · 2022Review
- The Hob proteins are novel and conserved lipid-binding proteins at ER-PM contact sites.Journal of cell science · 2022Article
- The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus.International journal of molecular sciences · 2021Article
- Insights into VPS13 properties and function reveal a new mechanism of eukaryotic lipid transport.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
- Suppression of Vps13 adaptor protein mutants reveals a central role for PI4P in regulating prospore membrane extension.PLoS genetics · 2021Article
- Genetic Dissection of Vps13 Regulation in Yeast Using Disease Mutations from Human Orthologs.International journal of molecular sciences · 2021Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The rare human disorder chorea-acanthocytosis (ChAc) is caused by mutations in hVPS13A gene. The hVps13A protein interacts with actin and regulates the level of phosphatidylinositol 4-phosphate (PI4P) in the membranes of neuronal cells. Yeast Vps13 is involved in vacuolar protein transport and, like hVps13A, participates in PI4P metabolism. Vps13 proteins are conserved in eukaryotes, but their molecular function remains unknown. One of the mutations found in ChAc patients causes amino acids substitution I2771R which affects the localization of hVps13A in skeletal muscles. To dissect the mechanism of pathogenesis of I2771R, we created and analyzed a yeast strain carrying the equivalent mutation. Here we show that in yeast, substitution I2749R causes dysfunction of Vps13 protein in endocytosis and vacuolar transport, although the level of the protein is not affected, suggesting loss of function. We also show that Vps13, like hVps13A, influences actin cytoskeleton organization and binds actin in immunoprecipitation experiments. Vps13-I2749R binds actin, but does not function in the actin cytoskeleton organization. Moreover, we show that Vps13 binds phospholipids, especially phosphatidylinositol 3-phosphate (PI3P), via its SHR_BD and APT1 domains. Substitution I2749R attenuates this ability. Finally, the localization of Vps13-GFP is altered when cellular levels of PI3P are decreased indicating its trafficking within the endosomal membrane system. These results suggest that PI3P regulates the functioning of Vps13, both in protein trafficking and actin cytoskeleton organization. Attenuation of PI3P-binding ability in the mutant hVps13A protein may be one of the reasons for its mislocalization and disrupted function in cells of patients suffering from ChAc.
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