4.5 Article

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

Journal

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2011.01.024

Keywords

Stress fiber; ROCK; Rho kinase; Myotonic dystrophy protein kinase; Actomyosin cytoskeleton; Myogenesis; Alternative splicing

Funding

  1. Prinses Beatrix Fonds
  2. Stichting Spieren voor Spieren
  3. Association Francaise contre les Myopathies (AFM)
  4. Muscular Dystrophy Association (MDA)

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DMPK, the product of the mutated gene in myotonic dystrophy type 1, belongs to the subfamily of Rho-associated serine-threonine protein kinases, whose members play a role in actin-based cell morphodynamics. Not much is known about the physiological role of differentially localized individual DMPK splice isoforms. We report here that prominent stellar-shaped stress fibers are formed during early and late steps of differentiation in DMPK-deficient myoblast-myotubes upon complementation with the short cytosolic DMPK E isoform. Expression of DMPK E led to an increased phosphorylation status of MLC2. We found no such effects with vectors that encode a mutant DMPK E which was rendered enzymatically inactive or any of the long C-terminally anchored DMPK isoforms. Presence of stellar structures appears associated with changes in cell shape and motility and a delay in myogenesis. Our data strongly suggest that cytosolic DMPK participates in remodeling of the actomyosin cytoskeleton in developing skeletal muscle cells. (C) 2011 Elsevier B.V. All rights reserved.

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