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

Authors

Katherine V. Bricceno, National Institutes of Health, Bethesda, MD
Tara Martinez, Johns Hopkins University
Evgenia Leikina, National Institutes of Health, Bethesda, MD
Stephanie Duguez, Children's National Medical Center
Terence A. Partridge, George Washington UniversityFollow
Leonid V. Chernomordik, National Institutes of Health, Bethesda, MD
Kenneth H. Fischbeck, National Institutes of Health, Bethesda, MD
Charlotte J. Sumner, Johns Hopkins University
Barrington G. Burnett, National Institutes of Health, Bethesda, MD

Document Type

Journal Article

Publication Date

4-18-2012

Journal

Human Molecular Genetics

Keywords

Focal Adhesions--metabolism; Muscle Development; Muscle Fibers, Skeletal--metabolism; Myogenin--genetics; Survival of Motor Neuron 1 Protein--metabolism

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.

Comments

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.

Creative Commons License

This work is free of known copyright restrictions.

APA Citation

Bricceno, V., Martinez, T., Leikina, E., Duguez, S., Partridge, T.A. et al. (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.

Peer Reviewed

1

Open Access

1