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

Katherine V. Bricceno, Tara Martinez, Evgenia Leikina, Stephanie Duguez, Terence A. Partridge, Leonid V. Chernomordik, Kenneth H. Fischbeck, Charlotte Sumner, Barrington G. Burnett

Research output: Contribution to journalArticle

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. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Original languageEnglish (US)
Article numberddu189
Pages (from-to)4745-4757
Number of pages13
JournalHuman Molecular Genetics
Volume23
Issue number18
DOIs
StatePublished - 2014

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Protein Deficiency
Focal Adhesions
Skeletal Muscle Fibers
Motor Neurons
Gene Expression
Muscle Cells
Spinal Muscular Atrophy
Muscle Development
Myoblasts
Muscles
Cell Movement
Myogenin
Nerve Degeneration
Membrane Fusion
Public Sector
Differentiation Antigens
Actin Cytoskeleton
Cell Membrane
Organizations
Cell Line

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology
  • Medicine(all)

Cite this

Bricceno, K. V., Martinez, T., Leikina, E., Duguez, S., Partridge, T. A., Chernomordik, L. V., ... Burnett, B. G. (2014). Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics. Human Molecular Genetics, 23(18), 4745-4757. [ddu189]. https://doi.org/10.1093/hmg/ddu189

Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics. / Bricceno, Katherine V.; Martinez, Tara; Leikina, Evgenia; Duguez, Stephanie; Partridge, Terence A.; Chernomordik, Leonid V.; Fischbeck, Kenneth H.; Sumner, Charlotte; Burnett, Barrington G.

In: Human Molecular Genetics, Vol. 23, No. 18, ddu189, 2014, p. 4745-4757.

Research output: Contribution to journalArticle

Bricceno, KV, Martinez, T, Leikina, E, Duguez, S, Partridge, TA, Chernomordik, LV, Fischbeck, KH, Sumner, C & Burnett, BG 2014, 'Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics', Human Molecular Genetics, vol. 23, no. 18, ddu189, pp. 4745-4757. https://doi.org/10.1093/hmg/ddu189
Bricceno, Katherine V. ; Martinez, Tara ; Leikina, Evgenia ; Duguez, Stephanie ; Partridge, Terence A. ; Chernomordik, Leonid V. ; Fischbeck, Kenneth H. ; Sumner, Charlotte ; Burnett, Barrington G. / Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 18. pp. 4745-4757.
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