ArticleProceedings of the National Academy of Sciences of the United States of America2022
A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at the plasma membrane.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 72 citations in OpenAlex.
- Endolysosomal iron-associated vesicular changes and ferroptosis-related vulnerability in VPS13A-knockdown cells.Molecular biology reports · 2026Article
- Article
- The Xkr protein family-From apoptosis executors to diverse physiological functions regulators.FEBS letters · 2026Review
- Brain Sphingolipid and Phospholipid Levels Are Altered in XK Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- An ER-IMC bridge protein TgVPS13A and an IMC-resident scramblase TgDAT1 drive daughter budding in Toxoplasma gondii.PLoS pathogens · 2026Article
- Four subtypes of disease-causing missense mutations underlie pathogenic protein interactions in neurodegenerative VPS13A disease.The Journal of clinical investigation · 2026Article
- VPS13A Deficiency Leads to Impaired Lipid Distribution and Alteration of Mitochondrial Calcium Homeostasis in Fibroblasts of VPS13A Disease Patients.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- A bridge-like lipid transfer protein is critical for generation of invasive stages in malaria parasites.Nature communications · 2026Article
- Mechanism of phospholipid transport to the bacterial outer membrane by TAM.bioRxiv : the preprint server for biology · 2026Article
- TMEM170 proteins are lipid scramblases associated with bridge-type lipid transporters BLTP1/Csf1.Nature structural & molecular biology · 2026Article
- The molecular mechanism of lipid uptake by membrane-anchored bridge-like lipid transfer proteins.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Diverse Neuromuscular Spectrum of VPS13A Disease.Annals of clinical and translational neurology · 2026Article
- Proceedings of the 12Tremor and other hyperkinetic movements (New York, N.Y.) · 2026Article
- A NovelInternational journal of molecular sciences · 2025Article
- Ist2 promotes lipid transfer by Osh6 via its membrane tethering and lipid scramblase activities.Science advances · 2025Article
- BLTP3A is associated with membranes of the late endocytic pathway and is an effector of CASM.The EMBO journal · 2025Article
- Neuropathological Characterisation of McLeod Syndrome With a Proposed New Grading System.Neuropathology and applied neurobiology · 2025Article
- Article
- Impaired hematopoiesis and embryonic lethality at midgestation of mice lacking both lipid transfer proteins VPS13A and VPS13C.PLoS biology · 2025Article
- Structure and function of the human apoptotic scramblase Xkr4.Nature communications · 2025Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Chorea-acanthocytosis (ChAc) and McLeod syndrome are diseases with shared clinical manifestations caused by mutations in VPS13A and XK, respectively. Key features of these conditions are the degeneration of caudate neurons and the presence of abnormally shaped erythrocytes. XK belongs to a family of plasma membrane (PM) lipid scramblases whose action results in exposure of PtdSer at the cell surface. VPS13A is an endoplasmic reticulum (ER)-anchored lipid transfer protein with a putative role in the transport of lipids at contacts of the ER with other membranes. Recently VPS13A and XK were reported to interact by still unknown mechanisms. So far, however, there is no evidence for a colocalization of the two proteins at contacts of the ER with the PM, where XK resides, as VPS13A was shown to be localized at contacts between the ER and either mitochondria or lipid droplets. Here we show that VPS13A can also localize at ER-PM contacts via the binding of its PH domain to a cytosolic loop of XK, that such interaction is regulated by an intramolecular interaction within XK, and that both VPS13A and XK are highly expressed in the caudate neurons. Binding of the PH domain of VPS13A to XK is competitive with its binding to intracellular membranes that mediate other tethering functions of VPS13A. Our findings support a model according to which VPS13A-dependent lipid transfer between the ER and the PM is coupled to lipid scrambling within the PM. They raise the possibility that defective cell surface exposure of PtdSer may be responsible for neurodegeneration.
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