Myotonic dystrophy protein kinase is involved in the modulation of the Ca2+ homeostasis in skeletal muscle cells.

Abstract

Myotonic dystrophy (DM), the most prevalent muscular disorder in adults, is caused by (CTG) n In conclusion, our data suggest that DMPK is involved in modulating the initial events of excitation-contraction coupling in skeletal muscle. (

Myotonic Dystrophy Protein Kinase: Structure, Function and Its Possible Role in the Pathogenesis of Myotonic Dystrophy Type 1

“…This effect demonstrates that conduction system is specifically compromised; supporting the idea that loss of DMPK plays a significant role in the cardiac DM1 phenotype Berul et al, 2000). DMPK deficit also cause an enhanced basal contractility of single cardiomyocytes with associated increase in intracellular Ca 2+ , suggesting that DMPK has a modulator role in the control of intracellular Ca 2+ concentration (Benders et al, 1997;Pall et al, 2003). In addition, hypophosphorylation of phospholamban (PLN), a muscle-specific sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2a) inhibitor, causes a deregulation of Ca 2+ uptake in sarcoplasmic reticulum vesicles of ventricular homogenates from DMPK -/-mice (Kaliman et al, 2005).…”

“…Transmembrane ion flux is the predominant factor in controlling the excitation-contraction coupling mechanism. Alteration in the function of voltage-dependent L-type Ca 2+ (the dihidropiridine receptor DHPR) and Na + channels has been shown in DMPK mice models (Benders et al, 1997), which evidences the importance of DMPK in the maintenance of this homeostasis. That is consistent with the fact that DHPR is a target of DMPK and that its activity is altered in DMPK -/-cells (Benders et al, 1997).…”

“…Electron microscopy analyses in adult rat spinal motor neurons reveal a localization of DMPK in the endoplasmic reticulum and dendritic microtubules, suggesting a function in membrane trafficking and secretion within neurons associated with cognition, memory, and motor control (Balasubramanyam et al, 1998). In addition, multiple subcellular localizations have been assigned to DMPK, including neuromuscular and myotendinous junctions Berul et al, 2000;Shimokawa et al, 1997) and terminal cisternae and intercalated discs of skeletal muscle sarcoplasmic reticulum (Benders et al, 1997;Pall et al, 2003;Saba et al, 1999). Furthermore, DMPK localization to gap junctions of the intercalated discs has been reported in the heart and Purkinje fibers (Kaliman et al, 2005;Mounsey et al, 2000b).…”

Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle

“…Several genes involved in Ca 2ϩ homeostasis had significantly altered expression patterns. ATP2A1, ANX7, CASQ2, DMPK, and HSBP2 are involved in Ca 2ϩ translocation from the cytosol to the sarcoplasmic reticulum lumen and in Ca 2ϩ homeostasis in muscle contraction (33)(34)(35). Their aberrant expression patterns suggest an overall increase of cytosolic Ca 2ϩ (Table 3).…”

Congenital Myotonic Dystrophy

“…The normal protein localizes to neuromuscular junctions [4], sarcoplasmic reticulum [5] and intercalated discs in the heart myocyte [6]. The functions of DMPK are manifold including: cell shape determination [4,7] and effects on excitation coupling through calcium homeostasis [8].…”