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alpha-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells.

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Abstract
Nemaline myopathy is a neuromuscular disorder, characterized by muscle weakness and hypotonia and is, in 20% of the cases, caused by mutations in the gene encoding alpha-skeletal muscle actin, ACTA1. It is a heterogeneous disease with various clinical phenotypes and severities. In patients the ultrastructure of muscle cells is often disturbed by nemaline rods and it is thought this is the cause for muscle weakness. To search for possible defects during muscle cell differentiation we expressed alpha-actin mutants in myoblasts and allowed these cells to differentiate into myotubes. Surprisingly, we observed two striking new phenotypes in differentiating myoblasts: rounding up of cells and bleb formation, two features reminiscent of apoptosis. Indeed expression of these mutants induced cell death with apoptotic features in muscle cell culture, using AIF and endonuclease G, in a caspase-independent but calpain-dependent pathway. This is the first report on a common cellular defect induced by NM causing actin mutants, independent of their biochemical phenotypes or rod and aggregate formation capacity. These data suggest that lack of type II fibers or atrophy observed in nemaline myopathy patients may be also due to an increased number of dying muscle cells.
Keywords
MUTATIONS, GENE ACTA1, MOUSE MODEL, INDUCED APOPTOSIS, CYTOSOLIC CHAPERONIN, Cell death, KeyWords Plus: BETA-ACTIN, Myotube, Myoblast, Actin, Nemaline myopathy, PROTEINS, RELEASE, DISEASE, AGE

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Chicago
Vandamme, Drieke, Ellen Lambert, DAVY WATERSCHOOT, C. Cognard, Joël Vandekerckhove, Christophe Ampe, B. Constantin, and Heidi Rommelaere. 2009. “alpha-Skeletal Muscle Actin Nemaline Myopathy Mutants Cause Cell Death in Cultured Muscle Cells.” Biochimica Et Biophysica Acta-molecular Cell Research 1793 (7): 1259–1271.
APA
Vandamme, D., Lambert, E., WATERSCHOOT, D., Cognard, C., Vandekerckhove, J., Ampe, C., Constantin, B., et al. (2009). alpha-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1793(7), 1259–1271.
Vancouver
1.
Vandamme D, Lambert E, WATERSCHOOT D, Cognard C, Vandekerckhove J, Ampe C, et al. alpha-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. AMSTERDAM, NETHERLANDS: Elsevier Science; 2009;1793(7):1259–71.
MLA
Vandamme, Drieke et al. “alpha-Skeletal Muscle Actin Nemaline Myopathy Mutants Cause Cell Death in Cultured Muscle Cells.” BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 1793.7 (2009): 1259–1271. Print.
@article{715852,
  abstract     = {Nemaline myopathy is a neuromuscular disorder, characterized by muscle weakness and hypotonia and is, in 20% of the cases, caused by mutations in the gene encoding alpha-skeletal muscle actin, ACTA1. It is a heterogeneous disease with various clinical phenotypes and severities. In patients the ultrastructure of muscle cells is often disturbed by nemaline rods and it is thought this is the cause for muscle weakness. To search for possible defects during muscle cell differentiation we expressed alpha-actin mutants in myoblasts and allowed these cells to differentiate into myotubes. Surprisingly, we observed two striking new phenotypes in differentiating myoblasts: rounding up of cells and bleb formation, two features reminiscent of apoptosis. Indeed expression of these mutants induced cell death with apoptotic features in muscle cell culture, using AIF and endonuclease G, in a caspase-independent but calpain-dependent pathway. This is the first report on a common cellular defect induced by NM causing actin mutants, independent of their biochemical phenotypes or rod and aggregate formation capacity. These data suggest that lack of type II fibers or atrophy observed in nemaline myopathy patients may be also due to an increased number of dying muscle cells.},
  author       = {Vandamme, Drieke and Lambert, Ellen and WATERSCHOOT, DAVY and Cognard, C. and Vandekerckhove, Joël and Ampe, Christophe and Constantin, B. and Rommelaere, Heidi},
  issn         = {0167-4889},
  journal      = {BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH},
  keywords     = {MUTATIONS,GENE ACTA1,MOUSE MODEL,INDUCED APOPTOSIS,CYTOSOLIC CHAPERONIN,Cell death,KeyWords Plus: BETA-ACTIN,Myotube,Myoblast,Actin,Nemaline myopathy,PROTEINS,RELEASE,DISEASE,AGE},
  language     = {eng},
  number       = {7},
  pages        = {1259--1271},
  publisher    = {Elsevier Science},
  title        = {alpha-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells.},
  url          = {http://dx.doi.org/10.1016/j.bbamcr.2009.04.004},
  volume       = {1793},
  year         = {2009},
}

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