ArticleNature communications2020
Rab35-regulated lipid turnover by myotubularins represses mTORC1 activity and controls myelin growth.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Lipid alterations in hereditary peripheral neuropathies: common mechanisms in disease heterogeneity?Molecular neurodegeneration · 2026Review
- Linc01271 promotes lipid synthesis and MASLD/MASH progression via miR-149-3p/RAB35 axis.Cellular and molecular life sciences : CMLS · 2025Article
- Rab35 Is Required for Embryonic Development and Kidney and Ureter Homeostasis through Regulation of Epithelial Cell Junctions.Journal of the American Society of Nephrology : JASN · 2024Article
- Peripheral Nervous System (PNS) Myelin Diseases.Cold Spring Harbor perspectives in biology · 2024Review
- Phosphoinositide switches in cell physiology - From molecular mechanisms to disease.The Journal of biological chemistry · 2024Review
- Role of SNAREs and Rabs in Myelin Regulation.International journal of molecular sciences · 2023Review
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Phosphoinositides as membrane organizers.Nature reviews. Molecular cell biology · 2022Review
- A Glance at the Molecules That Regulate Oligodendrocyte Myelination.Current issues in molecular biology · 2022Review
- Article
- Myelin Biology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Article
- Parkinson's Disease-Related Genes and Lipid Alteration.International journal of molecular sciences · 2021Review
- Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies.International journal of molecular sciences · 2021Review
- Dysregulation of myelin synthesis and actomyosin function underlies aberrant myelin in CMT4B1 neuropathy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A Golgi-associated lipid kinase controls peripheral nerve myelination.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inherited peripheral neuropathies (IPNs) represent a broad group of disorders including Charcot-Marie-Tooth (CMT) neuropathies characterized by defects primarily arising in myelin, axons, or both. The molecular mechanisms by which mutations in nearly 100 identified IPN/CMT genes lead to neuropathies are poorly understood. Here we show that the Ras-related GTPase Rab35 controls myelin growth via complex formation with the myotubularin-related phosphatidylinositol (PI) 3-phosphatases MTMR13 and MTMR2, encoded by genes responsible for CMT-types 4B2 and B1 in humans, and found that it downregulates lipid-mediated mTORC1 activation, a pathway known to crucially regulate myelin biogenesis. Targeted disruption of Rab35 leads to hyperactivation of mTORC1 signaling caused by elevated levels of PI 3-phosphates and to focal hypermyelination in vivo. Pharmacological inhibition of phosphatidylinositol 3,5-bisphosphate synthesis or mTORC1 signaling ameliorates this phenotype. These findings reveal a crucial role for Rab35-regulated lipid turnover by myotubularins to repress mTORC1 activity and to control myelin growth.
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