Myotonic dystrophy protein kinase (DMPK) induces actin cytoskeletal reorganization and apoptotic-like blebbing in lens cells

Misregulation of Alternative Splicing Causes Pathogenesis in Myotonic Dystrophy

“…All isoforms contain CTG repeats in the 3′ UTR except one isoform that splices out the repeats using an alternative splice acceptor site in exon 15 (Tiscornia and Mahadevan 2000). The biological function of DMPK is unknown, however, data suggest that DMPK protein might be involved in regulation of actin cytoskeleton (Jin et al 2000) and in calcium homeostasis (Kaliman et al 2005). In addition, specific DMPK splice variants localize to endoplasmic reticulum and mitochondrial membranes, and their presence causes ER and mitochondrial clustering (van Herpen et al 2005).…”

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

“…Phosphorylation of myosin phosphatase by DMPK promotes an increase in the phosphorylation state of myosin, which supports the assembly and contractility of the actin cytoskeleton (Muranyi et al, 2001). Thus, deregulation of DMPK expression could influences directly on actin cytoskeleton remodeling (Jin et al, 2000). These data together with abnormal LTP measures in a DMPK null mice (Schulz et al, 2003) suggest that DMPK have a key role in synaptic plasticity in such a way that DMPK depletion might contribute to the cognitive dysfunction associated with CDM, which is characterized by strong motor function and brain disability.…”

“…Overexpression of DMPK with enzymatic activity in epithelial lens cells led to apoptotic-like blebbing of plasma membrane and reorganization of the actin cytoskeleton. This may be relevant to the removal of membrane organelles, a necessary process during normal lens differentiation (Jin et al, 2000).…”

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].…”