ArticleHuman molecular genetics2020
A VPS13D spastic ataxia mutation disrupts the conserved adaptor-binding site in yeast Vps13.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Hoi1 targets BLTP2 to ER-PM contact sites to regulate lipid homeostasis.The Journal of cell biology · 2026Article
- Navigating the landscape of mitochondrial-ER communication in health and disease.Frontiers in molecular biosciences · 2024Review
- Orchestrating vesicular and nonvesicular membrane dynamics by intrinsically disordered proteins.EMBO reports · 2023Review
- The association of lipid transfer protein VPS13A with endosomes is mediated by sorting nexin SNX5.Life science alliance · 2023Article
- Endoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration.Cold Spring Harbor perspectives in biology · 2023Review
- In silico modeling human VPS13 proteins associated with donor and target membranes suggests lipid transfer mechanisms.Proteins · 2023Article
- A Novel Variant inBioMed research international · 2023Article
- Article
- Review
- Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome.Scientific reports · 2022Article
- Structural and biochemical insights into lipid transport by VPS13 proteins.The Journal of cell biology · 2022Article
- Lipid Dyshomeostasis and Inherited Cerebellar Ataxia.Molecular neurobiology · 2022Review
- Yeast as a Model to Find New Drugs and Drug Targets forInternational journal of molecular sciences · 2022Review
- Whole-exome sequencing confirms implication of VPS13D as a potential cause of progressive spastic ataxia.BMC neurology · 2022Article
- Sequence Analysis and Structural Predictions of Lipid Transfer Bridges in the Repeating Beta Groove (RBG) Superfamily Reveal Past and Present Domain Variations Affecting Form, Function and Interactions of VPS13, ATG2, SHIP164, Hobbit and Tweek.Contact (Thousand Oaks (Ventura County, Calif.)) · 2022Article
- A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing β-propeller protein-associated neurodegeneration.Human molecular genetics · 2021Article
- 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
- VPS13D bridges the ER to mitochondria and peroxisomes via Miro.The Journal of cell biology · 2021Article
- VPS13D promotes peroxisome biogenesis.The Journal of cell biology · 2021Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in each of the four human VPS13 (VPS13A-D) proteins are associated with distinct neurological disorders: chorea-acanthocytosis, Cohen syndrome, early-onset Parkinson's disease and spastic ataxia. Recent evidence suggests that the different VPS13 paralogs transport lipids between organelles at different membrane contact sites. How each VPS13 isoform is targeted to organelles is not known. We have shown that the localization of yeast Vps13 protein to membranes requires a conserved six-repeat region, the Vps13 Adaptor Binding (VAB) domain, which binds to organelle-specific adaptors. Here, we use a systematic mutagenesis strategy to determine the role of each repeat in recognizing each known adaptor. Our results show that mutation of invariant asparagines in repeats 1 and 6 strongly impacts the binding of all adaptors and blocks Vps13 membrane recruitment. However, we find that repeats 5-6 are sufficient for localization and interaction with adaptors. This supports a model where a single adaptor-binding site is found in the last two repeats of the VAB domain, while VAB domain repeat 1 may influence domain conformation. Importantly, a disease-causing mutation in VPS13D, which maps to the highly conserved asparagine residue in repeat 6, blocks adaptor binding and Vps13 membrane recruitment when modeled in yeast. Our findings are consistent with a conserved adaptor binding role for the VAB domain and suggest the presence of as-yet-unidentified adaptors in both yeast and humans.
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