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Hum Mol Genet. 2014 Sep 15;23(18):4745-57. doi: 10.1093/hmg/ddu189. Epub 2014 Apr 23.

Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics.

Author information

1
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke and Institute of Biomedical Sciences, The George Washington University, Washington, DC, USA.
2
Department of Neurology and.
3
Section on Membrane Biology, Program of Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
4
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
5
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke and.
6
Department of Neurology and Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA.
7
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke and Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, F. Edward Hebert School of Medicine, Bethesda, MD, USA bburnett@usuhs.edu.

Abstract

While spinal muscular atrophy (SMA) is characterized by motor neuron degeneration, it is unclear whether and how much survival motor neuron (SMN) protein deficiency in muscle contributes to the pathophysiology of the disease. There is increasing evidence from patients and SMA model organisms that SMN deficiency causes intrinsic muscle defects. Here we investigated the role of SMN in muscle development using muscle cell lines and primary myoblasts. Formation of multinucleate myotubes by SMN-deficient muscle cells is inhibited at a stage preceding plasma membrane fusion. We found increased expression and reduced induction of key muscle development factors, such as MyoD and myogenin, with differentiation of SMN-deficient cells. In addition, SMN-deficient muscle cells had impaired cell migration and altered organization of focal adhesions and the actin cytoskeleton. Partially restoring SMN inhibited the premature expression of muscle differentiation markers, corrected the cytoskeletal abnormalities and improved myoblast fusion. These findings are consistent with a role for SMN in myotube formation through effects on muscle differentiation and cell motility.

PMID:
24760765
PMCID:
PMC4140458
DOI:
10.1093/hmg/ddu189
[Indexed for MEDLINE]
Free PMC Article

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