title: Myotonic dystrophy kinase is a component of neuromuscular junctions.
abstract: The clinical manifestation of myotonic dystrophy (DM) is correlated to the extent of expansion of an unstable [CTG]n DNA motif. Recent studies have demonstrated that this trinucleotide motif forms part of the last, 3' untranslated exon of a gene which potentially encodes multiple protein isoforms of a serine/threonine protein kinase (myotonic dystrophy protein kinase, DM-PK). We report here on the development of antisera against synthetic DM-PK peptide antigens and their use in biochemical and histochemical studies. Immunoreactive DM-kinase protein of 53 kD is present at low levels in skeletal and cardiac muscle extracts of DM patients and normal controls. Immunohistochemical staining revealed that DM-PK is localised prominently at sites of neuromuscular and myotendinous junctions (NMJs and MTJs) of human and rodent skeletal muscles. Furthermore, very low levels of immunoreactive DM-PK protein are present in the sarcoplasm of predominantly type I fibres in various muscles. Strikingly, presence of the protein can also be demonstrated for NMJs of muscular tissues of adult and congenital cases of DM, with no gross changes in structural organisation. Our findings provide a basis for further characterisation of the role of the kinase in protein assembly processes or signal mediation at synaptic sites and ultimately for the understanding of the complex pathophysiology of DM.
authors.affiliation: Department of Cell Biology and Histology, Medical Faculty University Nijmegen, The Netherlands.
authors.forename: P F
authors.initials: PF
authors.lastname: van der Ven
authors.forename: G
authors.initials: G
authors.lastname: Jansen
authors.forename: T H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: M B
authors.initials: MB
authors.lastname: Perryman
authors.forename: M
authors.initials: M
authors.lastname: Lupa
authors.forename: P W
authors.initials: PW
authors.lastname: Dunne
authors.forename: H J
authors.initials: HJ
authors.lastname: ter Laak
authors.forename: P H
authors.initials: PH
authors.lastname: Jap
authors.forename: J H
authors.initials: JH
authors.lastname: Veerkamp
authors.forename: H F
authors.initials: HF
authors.lastname: Epstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology; D005091:Exons; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology*; D009223:Myotonic Dystrophy / Q000201:enzymology* / Q000235:genetics; D065636:Myotonin-Protein Kinase; D009469:Neuromuscular Junction / Q000201:enzymology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D000906:Antibodies; C585517:DMPK protein, human; C585516:DMPK protein, mouse; D010455:Peptides; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases