title: DMPK protein isoforms are differentially expressed in myogenic and neural cell lineages.
abstract: Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by an unstable (CTG . CAG)n segment in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. It is commonly accepted that DMPK mRNA-based toxicity is the main contributor to DM1 manifestations; however, not much is known about the significance of the DMPK protein. To appreciate its normal and possible pathobiological role, we analyzed the patterns of DMPK splice isoform expression in mouse tissues. Long membrane-anchored DMPK dominated in heart, diaphragm, and skeletal muscle, whereas short cytosolic isoforms were highly expressed in bladder and stomach. Both isoform types were present in diverse brain regions. DMPK protein was also detectable in cultured myoblasts, myotubes, cortical astrocytes, and related cell lines of neural or muscle origin, but not in hippocampal neurons. This work identifies DMPK as a kinase with pronounced expression in diverse muscle and neural tissues that are affected in DM1.
authors.affiliation: Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Ralph J A
authors.initials: RJ
authors.lastname: Oude Ophuis
authors.forename: Susan A M
authors.initials: SA
authors.lastname: Mulders
authors.forename: René E M A
authors.initials: RE
authors.lastname: van Herpen
authors.forename: Rinske
authors.initials: R
authors.lastname: van de Vorstenbosch
authors.forename: Bé
authors.initials: B
authors.lastname: Wieringa
authors.forename: Derick G
authors.initials: DG
authors.lastname: Wansink
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D019070:Cell Lineage / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007536:Isomerism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D032342:Muscle Cells / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D065636:Myotonin-Protein Kinase; D009474:Neurons / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
chemical_list: C585517:DMPK protein, human; C585516:DMPK protein, mouse; D012313:RNA; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases