MYOTONIC-DYSTROPHY KINASE IS A COMPONENT OF NEUROMUSCULAR-JUNCTIONS

The clinical manifestation of myotonic dystrophy (DM) is correlated to the extent of expansion of an unstable [CTG]n DNA motif. Recent studi es have demonstrated that this trinucleotide motif forms part of the l ast, 3' untranslated exon of a gene which potentially encodes multiple protein isoforms of a serine/threonine protein kinase (myotonic dystr ophy protein kinase, DM-PK). We report here on the development of anti sera against synthetic DM-PK peptide antigens and their use in biochem ical and histochemical studies. Immunoreactive DM-kinase protein of 53 kD is present at low levels in skeletal and cardiac muscle extracts o f DM patients and normal controls. Immunohistochemical staining reveal ed that DM-PK is localised prominently at sites of neuromuscular and m yotendinous junctions (NMJs and MTJs) of human and rodent skeletal mus cles. Furthermore, very low levels of immunoreactive DM-PK protein are present in the sarcoplasm of predominantly type I fibres in various m uscles. Strikingly, presence of the protein can also be demonstrated f or NMJs of muscular tissues of adult and congenital cases of DM, with no gross changes in structural organisation. Our findings provide a ba sis for further characterisation of the role of the kinase in protein assembly processes or signal mediation at synaptic sites and ultimatel y for the understanding of the complex pathophysiology of DM.