The intracellular Ca2+ channel MCOLN1 is required for sarcolemma repair to prevent muscular dystrophy (original) (raw)
- Letter
- Published: 14 September 2014
- Xiaoli Zhang1,
- Qiong Gao1,
- Mohammad Ali Samie1,
- Marlene Azar1,
- Wai Lok Tsang1,
- Libing Dong1,
- Nirakar Sahoo1,
- Xinran Li1,
- Yue Zhuo1,
- Abigail G Garrity1,2,
- Xiang Wang1,
- Marc Ferrer3,
- James Dowling4,5,6,7,8,
- Li Xu9,
- Renzhi Han9 &
- …
- Haoxing Xu1,2
Nature Medicine volume 20, pages 1187–1192 (2014)Cite this article
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Abstract
The integrity of the plasma membrane is maintained through an active repair process, especially in skeletal and cardiac muscle cells, in which contraction-induced mechanical damage frequently occurs in vivo1,2. Muscular dystrophies (MDs) are a group of muscle diseases characterized by skeletal muscle wasting and weakness3,4. An important cause of these group of diseases is defective repair of sarcolemmal injuries, which normally requires Ca2+ sensor proteins5,6,7,8 and Ca2+-dependent delivery of intracellular vesicles to the sites of injury8,9. MCOLN1 (also known as TRPML1, ML1) is an endosomal and lysosomal Ca2+ channel whose human mutations cause mucolipidosis IV (ML4), a neurodegenerative disease with motor disabilities10,11. Here we report that ML1-null mice develop a primary, early-onset MD independent of neural degeneration. Although the dystrophin-glycoprotein complex and the known membrane repair proteins are expressed normally, membrane resealing was defective in ML1-null muscle fibers and also upon acute and pharmacological inhibition of ML1 channel activity or vesicular Ca2+ release. Injury facilitated the trafficking and exocytosis of vesicles by upmodulating ML1 channel activity. In the dystrophic mdx mouse model, overexpression of ML1 decreased muscle pathology. Collectively, our data have identified an intracellular Ca2+ channel that regulates membrane repair in skeletal muscle via Ca2+-dependent vesicle exocytosis.
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References
- Clarke, M.S., Khakee, R. & McNeil, P.L. Loss of cytoplasmic basic fibroblast growth factor from physiologically wounded myofibers of normal and dystrophic muscle. J. Cell Sci. 106, 121–133 (1993).
CAS PubMed Google Scholar - McNeil, P.L. & Khakee, R. Disruptions of muscle fiber plasma membranes. Role in exercise-induced damage. Am. J. Pathol. 140, 1097–1109 (1992).
CAS PubMed PubMed Central Google Scholar - Davies, K.E. & Nowak, K.J. Molecular mechanisms of muscular dystrophies: old and new players. Nat. Rev. Mol. Cell Biol. 7, 762–773 (2006).
Article CAS Google Scholar - Rahimov, F. & Kunkel, L.M. The cell biology of disease: cellular and molecular mechanisms underlying muscular dystrophy. J. Cell Biol. 201, 499–510 (2013).
Article CAS Google Scholar - Bansal, D. et al. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 423, 168–172 (2003).
Article CAS Google Scholar - Chakrabarti, S. et al. Impaired membrane resealing and autoimmune myositis in synaptotagmin VII-deficient mice. J. Cell Biol. 162, 543–549 (2003).
Article CAS Google Scholar - Barresi, R. et al. LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies. Nat. Med. 10, 696–703 (2004).
Article CAS Google Scholar - McNeil, P. Membrane repair redux: redox of MG53. Nat. Cell Biol. 11, 7–9 (2009).
Article CAS Google Scholar - Cai, C. et al. MG53 nucleates assembly of cell membrane repair machinery. Nat. Cell Biol. 11, 56–64 (2009).
Article CAS Google Scholar - Sun, M. et al. Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel. Hum. Mol. Genet. 9, 2471–2478 (2000).
Article CAS Google Scholar - Venugopal, B. et al. Neurologic, gastric, and opthalmologic pathologies in a murine model of mucolipidosis type IV. Am. J. Hum. Genet. 81, 1070–1083 (2007).
Article CAS Google Scholar - Dong, X.P. et al. The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature 455, 992–996 (2008).
Article CAS Google Scholar - Shen, D. et al. Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release. Nat. Commun. 3, 731 (2012).
Article Google Scholar - Samie, M. et al. A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis. Dev. Cell 26, 511–524 (2013).
Article CAS Google Scholar - de Figueiredo, P. & Brown, W.J. A role for calmodulin in organelle membrane tubulation. Mol. Biol. Cell 6, 871–887 (1995).
Article CAS Google Scholar - Straub, V., Rafael, J.A., Chamberlain, J.S. & Campbell, K.P. Animal models for muscular dystrophy show different patterns of sarcolemmal disruption. J. Cell Biol. 139, 375–385 (1997).
Article CAS Google Scholar - Weitz, R. et al. Muscle involvement in mucolipidosis IV. Brain Dev. 12, 524–528 (1990).
Article CAS Google Scholar - Zlotogora, J., Ben Ezra, D., Livni, N., Ashkenazi, A. & Cohen, T. A muscle disorder as presenting symptom in a child with mucolipidosis IV. Neuropediatrics 14, 104–105 (1983).
Article CAS Google Scholar - Venugopal, B. et al. Chaperone-mediated autophagy is defective in mucolipidosis type IV. J. Cell. Physiol. 219, 344–353 (2009).
Article CAS Google Scholar - Abe, A. et al. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J. Clin. Invest. 105, 1563–1571 (2000).
Article CAS Google Scholar - Campbell, K.P. Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell 80, 675–679 (1995).
Article CAS Google Scholar - Cai, C. et al. Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3, and dysferlin. J. Biol. Chem. 284, 15894–15902 (2009).
Article CAS Google Scholar - Bansal, D. & Campbell, K.P. Dysferlin and the plasma membrane repair in muscular dystrophy. Trends Cell Biol. 14, 206–213 (2004).
Article CAS Google Scholar - Weisleder, N. et al. Recombinant MG53 protein modulates therapeutic cell membrane repair in treatment of muscular dystrophy. Sci. Transl. Med. 4, 139ra185 (2012).
Article Google Scholar - Idone, V. et al. Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis. J. Cell Biol. 180, 905–914 (2008).
Article CAS Google Scholar - Hua, Z. et al. v-SNARE composition distinguishes synaptic vesicle pools. Neuron 71, 474–487 (2011).
Article CAS Google Scholar - Reddy, A., Caler, E.V. & Andrews, N.W. Plasma membrane repair is mediated by Ca2+-regulated exocytosis of lysosomes. Cell 106, 157–169 (2001).
Article CAS Google Scholar - Corrotte, M. et al. Caveolae internalization repairs wounded cells and muscle fibers. Elife 2, e00926 (2013).
Article Google Scholar - Jimenez, A.J. et al. ESCRT machinery is required for plasma membrane repair. Science 343, 1247136 (2014).
Article Google Scholar - Demonbreun, A.R. et al. Impaired muscle growth and response to insulin-like growth factor 1 in dysferlin-mediated muscular dystrophy. Hum. Mol. Genet. 20, 779–789 (2011).
Article CAS Google Scholar - Bolsover, F.E., Murphy, E., Cipolotti, L., Werring, D.J. & Lachmann, R.H. Cognitive dysfunction and depression in Fabry disease: a systematic review. J. Inherit. Metab. Dis. 37, 177–187 (2014).
Article Google Scholar - Springer, M.L., Rando, T.A. & Blau, H.M. Gene delivery to muscle. Curr. Protoc. Hum. Genet. 31, 13.14 (2002).
Google Scholar - Dong, X.P. et al. PI3,5P2 controls membrane traffic by direct activation of mucolipin Ca release channels in the endolysosome. Nat. Commun. 1, 38 (2010).
Article Google Scholar - Wang, X. et al. TPC proteins are phosphoinositide-activated sodium-selective ion channels in endosomes and lysosomes. Cell 151, 372–383 (2012).
Article CAS Google Scholar - Brooke, M.H. & Kaiser, K.K. Muscle fiber types: how many and what kind? Arch. Neurol. 23, 369–379 (1970).
Article CAS Google Scholar
Acknowledgements
This work was supported by National Institutes of Health (NIH) grants (NS062792, MH096595 and AR060837 to H.X.; HL116546 and AR064241 to R.H.). We are grateful to S. Slaugenhaupt for the ML1 KO mice, L. Looger for the GCaMP3 construct, R. Edwards for the Vamp7-pHluorin construct, the Center for Live-Cell Imaging at the University of Michigan for the help on TIRF Imaging, and R. Hume and M. Akaaboune for comments on the manuscript. We appreciate the encouragement and helpful comments of other members of the Xu laboratory.
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Authors and Affiliations
- Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA
Xiping Cheng, Xiaoli Zhang, Qiong Gao, Mohammad Ali Samie, Marlene Azar, Wai Lok Tsang, Libing Dong, Nirakar Sahoo, Xinran Li, Yue Zhuo, Abigail G Garrity, Xiang Wang & Haoxing Xu - Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan, USA
Abigail G Garrity & Haoxing Xu - National Center for Advancing Translational Science, National Institutes of Health, Maryland, USA
Marc Ferrer - Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan, USA
James Dowling - Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada
James Dowling - Program of Genetic and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada,
James Dowling - Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada,
James Dowling - Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
James Dowling - Department of Cell and Molecular Physiology, Loyola University Chicago Health Sciences Division, Chicago, Illinois, USA
Li Xu & Renzhi Han
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Contributions
X.C. initiated the project; H.X., X.C., J.D. and R.H. designed the research; X.C., X.Z., Q.G., M.A.S., M.A., W.L.T., Y.Z. and L.D. performed the research; N.S., X.L., A.G.G., X.W., M.F. and L.X. contributed the new reagents; X.C., X.Z., Q.G., M.A.S., M.A., W.L.T., J.D., R.H. and H.X. analyzed the data; H.X. and X.C. wrote the paper with input from all the authors.
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Correspondence toXiping Cheng or Haoxing Xu.
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Cheng, X., Zhang, X., Gao, Q. et al. The intracellular Ca2+ channel MCOLN1 is required for sarcolemma repair to prevent muscular dystrophy.Nat Med 20, 1187–1192 (2014). https://doi.org/10.1038/nm.3611
- Received: 05 March 2014
- Accepted: 19 May 2014
- Published: 14 September 2014
- Issue Date: October 2014
- DOI: https://doi.org/10.1038/nm.3611