ArticleProceedings of the National Academy of Sciences of the United States of America2016
Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-Golgi junctions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed.
- Phosphatidylserine and RhoB connect PI4P and PA metabolism to maintain plasma membrane identity.The Journal of cell biology · 2026Article
- Approaches to visualize, quantify, and manipulate phosphoinositides in cells.Histochemistry and cell biology · 2026Review
- Phosphatidylserine and RhoB connect phosphatidylinositol 4-phosphate and phosphatidic acid metabolism at the plasma membrane.bioRxiv : the preprint server for biology · 2025Article
- The Inner Nuclear Membrane Has a Unique Lipid Signature.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids.The Journal of cell biology · 2025Article
- Phosphoinositide Metabolism: Biochemistry, Physiology and Genetic Disorders.Journal of inherited metabolic disease · 2025Review
- The dynamic regulatory network of phosphatidic acid metabolism: a spotlight on substrate cycling between phosphatidic acid and diacylglycerol.Biochemical Society transactions · 2024Review
- Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis.The EMBO journal · 2024Article
- Non-vesicular phosphatidylinositol transfer plays critical roles in defining organelle lipid composition.The EMBO journal · 2024Article
- Phosphatidylserine synthesis controls oncogenic B cell receptor signaling in B cell lymphoma.The Journal of cell biology · 2024Article
- Orthogonal targeting of SAC1 to mitochondria implicates ORP2 as a major player in PM PI4P turnover.bioRxiv : the preprint server for biology · 2024Article
- Reconstitution of ORP-mediated lipid exchange process coupled to PI(4)P metabolism.bioRxiv : the preprint server for biology · 2023Article
- Creating and sensing asymmetric lipid distributions throughout the cell.Emerging topics in life sciences · 2023Article
- High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Review
- Roles of Phosphatidylinositol 4-Phosphorylation in Non-vesicular Cholesterol Trafficking.Advances in experimental medicine and biology · 2023Article
- The ultrastructural organization of endoplasmic reticulum-plasma membrane contacts is conserved in epithelial cells.Molecular biology of the cell · 2022Article
- LIPID transfer proteins regulate store-operated calcium entry via control of plasma membrane phosphoinositides.Cell calcium · 2022Article
- The involvement of oxysterol-binding protein related protein (ORP) 6 in the counter-transport of phosphatidylinositol-4-phosphate (PI4P) and phosphatidylserine (PS) in neurons.Biochemistry and biophysics reports · 2022Article
- De novo loss-of-function variant in PTDSS1 is associated with developmental delay.American journal of medical genetics. Part A · 2022Article
- Metabolic changes induced by TGF-β1 via reduced expression of phosphatidylserine decarboxylase during myofibroblast transition.Journal of clinical biochemistry and nutrition · 2022Article
3 more citing papers are in PubMed but not listed here.
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7 authors.
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Abstract
Lenz-Majewski syndrome (LMS) is a rare disease characterized by complex craniofacial, dental, cutaneous, and limb abnormalities combined with intellectual disability. Mutations in thePTDSS1gene coding one of the phosphatidylserine (PS) synthase enzymes, PSS1, were described as causative in LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS levels. Here we show that expression of mutant PSS1 enzymes decreased phosphatidylinositol 4-phosphate (PI4P) levels both in the Golgi and the plasma membrane (PM) by activating the Sac1 phosphatase and altered PI4P cycling at the PM. Conversely, inhibitors of PI4KA, the enzyme that makes PI4P in the PM, blocked PS synthesis and reduced PS levels by 50% in normal cells. However, mutant PSS1 enzymes alleviated the PI4P dependence of PS synthesis. Oxysterol-binding protein-related protein 8, which was recently identified as a PI4P-PS exchanger between the ER and PM, showed PI4P-dependent membrane association that was significantly decreased by expression of PSS1 mutant enzymes. Our studies reveal that PS synthesis is tightly coupled to PI4P-dependent PS transport from the ER. Consequently, PSS1 mutations not only affect cellular PS levels and distribution but also lead to a more complex imbalance in lipid homeostasis by disturbing PI4P metabolism.
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