ArticleEMBO reports2021
OCRL regulates lysosome positioning and mTORC1 activity through SSX2IP-mediated microtubule anchoring.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Modeling of Lowe Patient-Derived Induced Pluripotent Stem Cells Into Trabecular Meshwork.American journal of ophthalmology · 2026Article
- CRISPR and Gene Augmentation Rescue Trabecular Meshwork Dysfunction in iPSC Models of Lowe Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lipid turnover and GEF recruitment collectively determine Rab5 recruitment and activation during the first step of early endosome formation.Nature communications · 2026Article
- Article
- Planar polarization of endogenous ADIP during Xenopus neurulation.Biology open · 2026Article
- Peripheral lysosome levels dictate mTORC1 inactivation even when catabolically impaired.Cell communication and signaling : CCS · 2026Article
- Bleeding and hemostatic defects in Lowe syndrome: the role of OCRL in platelets.Frontiers in cell and developmental biology · 2026Review
- Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer's Disease: Implications for Autophagy Dysfunction.International journal of molecular sciences · 2025Article
- TRPML-1 Dysfunction and Renal Tubulopathy in Mucolipidosis Type IV.Journal of the American Society of Nephrology : JASN · 2025Article
- Matrix stiffness regulates mitochondria-lysosome contacts to modulate the mitochondrial network, alleviate the senescence of MSCs.Cell proliferation · 2025Article
- Bidirectional crosstalk between the bone extracellular matrix and lysosomes in bone remodeling and osteoporosis.Frontiers in endocrinology · 2025Review
- OCRL1 Deficiency Affects the Intracellular Traffic of ApoER2 and Impairs Reelin-Induced Responses.Biomolecules · 2024Article
- Base editing correction of OCRL in Lowe syndrome: ABE-mediated functional rescue in patient-derived fibroblasts.Human molecular genetics · 2024Article
- Defining a cohort of anemia-activated cis elements reveals a mechanism promoting erythroid precursor function.Blood advances · 2023Article
- NovelFrontiers in endocrinology · 2023Article
- Branched-Chain Amino Acids and Insulin Resistance, from Protein Supply to Diet-Induced Obesity.Nutrients · 2022Review
- Assessment of endocytic traffic and Ocrl function in the developing zebrafish neuroepithelium.Journal of cell science · 2022Article
- A combinedCell cycle (Georgetown, Tex.) · 2022Article
- Participation of OCRL1, and APPL1, in the expression, proteolysis, phosphorylation and endosomal trafficking of megalin: Implications for Lowe Syndrome.Frontiers in cell and developmental biology · 2022Article
- OCRL regulates lysosome positioning and mTORC1 activity through SSX2IP-mediated microtubule anchoring.EMBO reports · 2021Article
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9 authors at 2 institutions in 1 country.
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Abstract
Lysosomal positioning and mTOR (mammalian target of rapamycin) signaling coordinate cellular responses to nutrient levels. Inadequate nutrient sensing can result in growth delays, a hallmark of Lowe syndrome. OCRL mutations cause Lowe syndrome, but the role of OCRL in nutrient sensing is unknown. Here, we show that OCRL is localized to the centrosome by its ASH domain and that it recruits microtubule-anchoring factor SSX2IP to the centrosome, which is important in the formation of the microtubule-organizing center. Deficiency of OCRL in human and mouse cells results in loss of microtubule-organizing centers and impaired microtubule-based lysosome movement, which in turn leads to mTORC1 inactivation and abnormal nutrient sensing. Centrosome-targeted PACT-SSX2IP can restore microtubule anchoring and mTOR activity. Importantly, boosting the activity of mTORC1 restores the nutrient sensing ability of Lowe patients' cells. Our findings highlight mTORC1 as a novel therapeutic target for Lowe syndrome.
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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.