NOVEL ISOFORM OF MYOTONIN PROTEIN-KINASE - GENE-PRODUCT OF MYOTONIC-DYSTROPHY IS LOCALIZED IN THE SARCOPLASMIC-RETICULUM OF SKELETAL-MUSCLE

It is quite important to know the exact localization and function of m yotonin protein kinase (MtPK), identified as the gene product of myoto nic dystrophy, the most prevalent disease with multisystem disorders a mong muscular dystrophies. To investigate the localization of MtPK, we raised a polyclonal antibody against a synthetic peptide chosen withi n the deduced sequence of MtPK. This antibody detected both a membrane -bound 70-kd protein and a soluble 55-kd protein on Western blots of h uman muscles. By using this antibody for immunohistochemical studies o f both biopsied human skeletal muscle fibers and mature innervated cul tured muscle fibers, we can now demonstrate by confocal laser scanning microscopy that MtPK is localized mainly in the I-band. By immunoelec tron microscopy, it was determined that MtPK is a membrane-bound prote in localized mainly in the terminal cisternae of the sarcoplasmic reti culum. To our knowledge, this is the first documentation of the ultras tructural localization of MtPK. This finding is quite important for cl arifying the pathophysiological basis of myotonic dystrophy, which mig ht be due to a dysregulation of calcium metabolism.