ArticlePLoS genetics2012
Phosphatase-dead myotubularin ameliorates X-linked centronuclear myopathy phenotypes in mice.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
- Lack of myotubularin phosphatase activity is the main cause of X-linked myotubular myopathy.JCI insight · 2025Article
- Lactate-induced activation of tumor-associated fibroblasts and IL-8-mediated macrophage recruitment promote lung cancer progression.Redox biology · 2024Article
- Integrated multi-omics approach reveals the role of striated muscle preferentially expressed protein kinase in skeletal muscle including its relationship with myospryn complex.Journal of cachexia, sarcopenia and muscle · 2024Article
- Article
- MTM1 overexpression prevents and reverts BIN1-related centronuclear myopathy.Brain : a journal of neurology · 2023Article
- Structural rationale to understand the effect of disease-associated mutations on Myotubularin.Current research in structural biology · 2023Article
- The Sarcoplasmic Reticulum of Skeletal Muscle Cells: A Labyrinth of Membrane Contact Sites.Biomolecules · 2022Review
- Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances.International journal of molecular sciences · 2021Review
- Differential physiological roles for BIN1 isoforms in skeletal muscle development, function and regeneration.Disease models & mechanisms · 2020Article
- Roles for a lipid phosphatase in the activation of its opposing lipid kinase.Molecular biology of the cell · 2020Article
- De novo phosphoinositide synthesis in zebrafish is required for triad formation but not essential for myogenesis.PloS one · 2020Article
- Phosphoinositides in autophagy: current roles and future insights.The FEBS journal · 2020Review
- The expanding spectrum of neurological disorders of phosphoinositide metabolism.Disease models & mechanisms · 2019Review
- Recessive PYROXD1 mutations cause adult-onset limb-girdle-type muscular dystrophy.Journal of neurology · 2019Article
- Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy.Nature communications · 2018Article
- Centronuclear myopathies under attack: A plethora of therapeutic targets.Journal of neuromuscular diseases · 2018Review
- Amphiphysin (BIN1) negatively regulates dynamin 2 for normal muscle maturation.The Journal of clinical investigation · 2017Article
- Antisense oligonucleotide-mediated Dnm2 knockdown prevents and reverts myotubular myopathy in mice.Nature communications · 2017Article
- A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi.Nature communications · 2016Article
- Variants in the Oxidoreductase PYROXD1 Cause Early-Onset Myopathy with Internalized Nuclei and Myofibrillar Disorganization.American journal of human genetics · 2016Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myotubularin MTM1 is a phosphoinositide (PPIn) 3-phosphatase mutated in X-linked centronuclear myopathy (XLCNM; myotubular myopathy). We investigated the involvement of MTM1 enzymatic activity on XLCNM phenotypes. Exogenous expression of human MTM1 in yeast resulted in vacuolar enlargement, as a consequence of its phosphatase activity. Expression of mutants from patients with different clinical progression and determination of PtdIns3P and PtdIns5P cellular levels confirmed the link between vacuolar morphology and MTM1 phosphatase activity, and showed that some disease mutants retain phosphatase activity. Viral gene transfer of phosphatase-dead myotubularin mutants (MTM1(C375S) and MTM1(S376N)) significantly improved most histological signs of XLCNM displayed by a Mtm1-null mouse, at similar levels as wild-type MTM1. Moreover, the MTM1(C375S) mutant improved muscle performance and restored the localization of nuclei, triad alignment, and the desmin intermediate filament network, while it did not normalize PtdIns3P levels, supporting phosphatase-independent roles of MTM1 in maintaining normal muscle performance and organelle positioning in skeletal muscle. Among the different XLCNM signs investigated, we identified only triad shape and fiber size distribution as being partially dependent on MTM1 phosphatase activity. In conclusion, this work uncovers MTM1 roles in the structural organization of muscle fibers that are independent of its enzymatic activity. This underlines that removal of enzymes should be used with care to conclude on the physiological importance of their activity.
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