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Abnormal actomyosin assembly in proliferating and differentiating myoblasts upon expression of a cytosolic DMPK

Susan A M Mulders1, Remco van Horssen, Lieke Gerrits

  • 1Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. s.mulders@ncmls.nl

Biochimica Et Biophysica Acta
|February 8, 2011
PubMed

Insights

The short cytosolic DMPK E isoform, linked to myotonic dystrophy type 1, rebuilds muscle cell actin cytoskeleton. This impacts cell shape, motility, and delays muscle development.

Area of Science:

  • Cell Biology
  • Muscle Physiology
  • Biochemistry

Background:

  • Myotonic dystrophy type 1 is caused by mutations in the DMPK gene.
  • DMPK (dystrophia myotonica-protein kinase) is a serine-threonine kinase involved in cell morphodynamics.
  • The specific roles of DMPK splice isoforms are not well understood.

Purpose of the Study:

  • To investigate the physiological role of the short cytosolic DMPK E isoform.
  • To determine the effects of DMPK E on myoblast-myotube differentiation and actomyosin cytoskeleton.
  • To explore the impact of DMPK E's enzymatic activity and localization on these processes.

Main Methods:

  • Complementation of DMPK-deficient myoblasts with DMPK E isoforms.
  • Analysis of stress fiber formation and cell morphology.
  • Assessment of myosin light chain 2 (MLC2) phosphorylation.
  • Comparison with enzymatically inactive DMPK E and long DMPK isoforms.

Main Results:

  • DMPK E expression induced prominent stellar-shaped stress fibers during myoblast differentiation.
  • DMPK E increased the phosphorylation status of MLC2.
  • Enzymatically inactive DMPK E and long DMPK isoforms did not produce these effects.
  • Stellar structures correlated with altered cell shape, motility, and delayed myogenesis.

Conclusions:

  • Cytosolic DMPK E isoform plays a key role in actomyosin cytoskeleton remodeling in skeletal muscle cells.
  • DMPK E's kinase activity is crucial for its effects on cytoskeleton and myogenesis.
  • These findings shed light on the function of DMPK isoforms in muscle development and disease.

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