ArticleMolecular biology of the cell2008
Sequential actions of myotubularin lipid phosphatases regulate endosomal PI(3)P and growth factor receptor trafficking.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01840657 (Prospective Study of Adverse Event Rates in Males With X-Linked Myotubular Myopathy), which is not on this map. Cited by 79 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Prospective Study of Adverse Event Rates in Males With X-Linked Myotubular Myopathy
Who cites it
79 citing papers in PubMed, 143 citations in OpenAlex.
- Phosphoinositide Depletion and Compensatory Phospho-Signaling in Angiotensin II-Induced Heart Disease.Circulation research · 2026Article
- MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids.The Journal of cell biology · 2025Article
- Structural insights into Beclin 1 interactions with it's regulators for autophagy modulation.Computational and structural biotechnology journal · 2025Review
- Recent advances of myotubularin-related (MTMR) protein family in cardiovascular diseases.Frontiers in cardiovascular medicine · 2024Review
- Loss of Mtm1 causes cholestatic liver disease in a model of X-linked myotubular myopathy.The Journal of clinical investigation · 2023Article
- Machine learning-based solution reveals cuproptosis features in inflammatory bowel disease.Frontiers in immunology · 2023Article
- Intrahepatic Cholestasis Is a Clinically Significant Feature Associated with Natural History of X-Linked Myotubular Myopathy (XLMTM): A Case Series and Biopsy Report.Journal of neuromuscular diseases · 2022Article
- Regulation of Neutrophil NADPH Oxidase, NOX2: A Crucial Effector in Neutrophil Phenotype and Function.Frontiers in cell and developmental biology · 2022Review
- INCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy.Journal of neuromuscular diseases · 2022Article
- Condition-dependent functional shift of twoAutophagy · 2021Article
- Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances.International journal of molecular sciences · 2021Review
- Modulation of phagosome phosphoinositide dynamics by a Legionella phosphoinositide 3-kinase.EMBO reports · 2021Article
- Rapid removal of phagosomal ferroportin in macrophages contributes to nutritional immunity.Blood advances · 2021Article
- Held Up in Traffic-Defects in the Trafficking Machinery in Charcot-Marie-Tooth Disease.Frontiers in molecular neuroscience · 2021Review
- From Mice to Humans: An Overview of the Potentials and Limitations of Current Transgenic Mouse Models of Major Muscular Dystrophies and Congenital Myopathies.International journal of molecular sciences · 2020Review
- Severe Consequences of SAC3/FIG4 Phosphatase Deficiency to Phosphoinositides in Patients with Charcot-Marie-Tooth Disease Type-4J.Molecular neurobiology · 2019Article
- The expanding spectrum of neurological disorders of phosphoinositide metabolism.Disease models & mechanisms · 2019Review
- Higher-order assembly of Sorting Nexin 16 controls tubulation and distribution of neuronal endosomes.The Journal of cell biology · 2019Article
- Article
- Vps34/PI3KC3 deletion in kidney proximal tubules impairs apical trafficking and blocks autophagic flux, causing a Fanconi-like syndrome and renal insufficiency.Scientific reports · 2018Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Two different human diseases, X-linked myotubular myopathy and Charcot-Marie-Tooth disease, result from mutant MTM1 or MTMR2 lipid phosphatases. Although events involved in endosomal PI(3)P and PI(3,5)P(2) synthesis are well established and pivotal in receptor signaling and degradation, enzymes involved in phosphoinositide degradation and their roles in trafficking are incompletely characterized. Here, we dissect the functions of the MTM1 and MTMR2 myotubularins and establish how they contribute to endosomal PI(3)P homeostasis. By mimicking loss of function in disease through siRNA-mediated depletion of the myotubularins, excess PI(3)P accumulates on early (MTM1) and late (MTMR2) endosomes. Surprisingly, the increased PI(3)P blocks the egress of epidermal growth factor receptors from early or late endosomes, suggesting that the accumulation of signaling receptors in distinct endosomes may contribute to the unique disease etiologies when MTM1 or MTMR2 are mutant. We further demonstrate that direct myotubularin binding to the type III PI 3-kinase complex hVps34/hVps15 leads to phosphatase inactivation. The lipid kinase-phosphatase interaction also precludes interaction of the PI 3-kinase with Rab GTPase activators. Thus, unique molecular complexes control kinase and phosphatase activation and locally regulate PI(3)P on discrete endosome populations, thereby providing a molecular rationale for related human myo- and neuropathies.
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Registered trials
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.