title: Abnormal actomyosin assembly in proliferating and differentiating myoblasts upon expression of a cytosolic DMPK isoform.
abstract: 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. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
authors.affiliation: Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. s.mulders@ncmls.nl
authors.forename: Susan A M
authors.initials: SA
authors.lastname: Mulders
authors.forename: Remco
authors.initials: R
authors.lastname: van Horssen
authors.forename: Lieke
authors.initials: L
authors.lastname: Gerrits
authors.forename: Miranda B
authors.initials: MB
authors.lastname: Bennink
authors.forename: Helma
authors.initials: H
authors.lastname: Pluk
authors.forename: Roelie T
authors.initials: RT
authors.lastname: de Boer-van Huizen
authors.forename: Huib J E
authors.initials: HJ
authors.lastname: Croes
authors.forename: Mietske
authors.initials: M
authors.lastname: Wijers
authors.forename: Fons A J
authors.initials: FA
authors.lastname: van de Loo
authors.forename: Jack
authors.initials: J
authors.lastname: Fransen
authors.forename: Bé
authors.initials: B
authors.lastname: Wieringa
authors.forename: Derick G
authors.initials: DG
authors.lastname: Wansink
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D016764:Cell Polarity; D049109:Cell Proliferation; D048430:Cell Shape; D003600:Cytosol / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology* / Q000201:enzymology*; D024462:Myosin Type II / Q000378:metabolism; D065636:Myotonin-Protein Kinase; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D022502:Stress Fibers / Q000378:metabolism / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000199:Actins; C585516:DMPK protein, mouse; D007527:Isoenzymes; D000205:Actomyosin; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; D024462:Myosin Type II