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 J Sumner, Barrington G Burnett

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    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.
    LanguageEnglish
    Pages4745-4757
    Number of pages12
    JournalHuman Molecular Genetics
    Volume23
    Issue number18
    Early online date23 Apr 2014
    DOIs
    Publication statusE-pub ahead of print - 23 Apr 2014

    Fingerprint

    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
    Differentiation Antigens
    Actin Cytoskeleton
    Cell Membrane
    Cell Line

    Keywords

    • SMN
    • Mice
    • myoblast fusion

    Cite this

    Bricceno, Katherine V ; Martinez, Tara ; Leikina, Evgenia ; Duguez, Stephanie ; Partridge, Terence A ; Chernomordik, Leonid V ; Fischbeck, Kenneth H ; Sumner, Charlotte J ; 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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    Bricceno, KV, Martinez, T, Leikina, E, Duguez, S, Partridge, TA, Chernomordik, LV, Fischbeck, KH, Sumner, CJ & 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, pp. 4745-4757. 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 J; Burnett, Barrington G.

    In: Human Molecular Genetics, Vol. 23, No. 18, 23.04.2014, p. 4745-4757.

    Research output: Contribution to journalArticle

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    AU - Duguez, Stephanie

    AU - Partridge, Terence A

    AU - Chernomordik, Leonid V

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