In situ hybridization analysis of Dmpk mRNA in adult mouse tissues

Sarkar, Partha S.; Han, Jennifer; Reddy, Sita

doi:10.1016/j.nmd.2004.03.012

Cited by 36 publications

(33 citation statements)

References 39 publications

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“…Skeletal and cardiac muscle, as well as smooth muscle in the gut and lung, are positive for the dmpk signal in mouse embryos. This is in agreement with a recent report (38) describing the expression pattern of dmpk in adult tissues. In the developing heart, we did not detect a hybridization signal in the epicardium or in the endocardium, suggesting that DMPK is primarily restricted to the contractile muscle.…”

Section: Discussionsupporting

confidence: 94%

Myotonic Dystrophy Protein Kinase Phosphorylates Phospholamban and Regulates Calcium Uptake in Cardiomyocyte Sarcoplasmic Reticulum

Kaliman

Catalucci

Lam

et al. 2005

Journal of Biological Chemistry

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Myotonic dystrophy (DM) is caused by a CTG expansion in the 3-untranslated region of a protein kinase gene (DMPK). Cardiovascular disease is one of the most prevalent causes of death in DM patients. Electrophysiological studies in cardiac muscles from DM patients and from DMPK ؊/؊ mice suggested that DMPK is critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity. However, there are no data regarding the molecular signaling pathways involved in DM heart failure. Here we show that DMPK expression in cardiac myocytes is highly enriched in the sarcoplasmic reticulum (SR) where it colocalizes with the ryanodine receptor and phospholamban (PLN), a muscle-specific SR Ca 2؉ -ATPase (SERCA2a) inhibitor. Coimmunoprecipitation studies showed that DMPK and PLN can physically associate. Furthermore, purified wild-type DMPK, but not a kinase-deficient mutant (K110A DMPK), phosphorylates PLN in vitro. Subsequent studies using the DMPK ؊/؊ mice demonstrated that PLN is hypo-phosphorylated in SR vesicles from DMPK ؊/؊ mice compared with wild-type mice both in vitro and in vivo. Finally, we show that Ca 2؉ uptake in SR is impaired in ventricular homogenates from DMPK ؊/؊ mice. Together, our data suggest the existence of a novel regulatory DMPK pathway for cardiac contractility and provide a molecular mechanism for DM heart pathology. Myotonic muscular dystrophy (DM)1 is an autosomal, dominant inherited, neuromuscular disorder with an incidence of 1 in 8000 in European and North American populations. Clinical expression of DM is extremely variable; patients present with progressive muscular dystrophy associated with the inability to promote normal muscle relaxation (myotonia), cataracts, cardiac arrhythmia, testicular atrophy, and insulin resistance (1).The DM1 mutation has been identified as the expansion of an unstable CTG repeat in the 3Ј-untranslated region of a gene encoding myotonic dystrophy protein kinase (DMPK) at chromosome 19q13.3. The age of onset and the severity of the disease correlate with the extent of expansion (2, 3). The dmpk gene product is a Ser/Thr protein kinase homologous to the MRCK p21-activated kinases (4) and the Rho family of kinases (5). Data obtained by using antibodies that detect specific isoforms of DMPK indicate that the most abundant isoform of DMPK is an 80-kDa protein expressed almost exclusively in smooth, skeletal, and cardiac muscles (6). This kinase exists both as a membrane-associated and as a soluble form in human left ventricular samples (7). The different C termini of DMPK that arise from alternative splicing determine its localization to the endoplasmic reticulum, mitochondria, or cytosol in transfected COS-1 cells (8). Among the substrates for DMPK proposed by in vitro studies are phospholemman, the dihydropyridine receptor, and the myosin phosphatase targeting subunit (9 -11). However, an in vivo demonstration of the phosphorylation of these substrates by DMPK remains to be established, and a link between these substrates an...

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Section: Discussionsupporting

confidence: 94%

Myotonic Dystrophy Protein Kinase Phosphorylates Phospholamban and Regulates Calcium Uptake in Cardiomyocyte Sarcoplasmic Reticulum

Kaliman

Catalucci

Lam

et al. 2005

Journal of Biological Chemistry

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“…Myotonic dystrophy 1 is a multisystem disorder resulting from a CTG repeat expansion located in the 3 0 untranslated region of the gene for dystrophia myotonica-protein kinase (DMPK) . Although DMPK mRNA is found in testis where it is expressed in all germ cells, Dmpk 2/2 mice do not show any testicular defects (Sarkar et al, 2004).…”

Section: Homeobox Factorsmentioning

confidence: 90%

“…Absence of Six5 gene expression has no effect on the testis of mice until postnatal day 14. Thereafter extensive apoptosis of germ cells as well as a block in spermiogenesis occurs resulting in male sterility (Sarkar et al, 2004). Myotonic dystrophy 1 is a multisystem disorder resulting from a CTG repeat expansion located in the 3 0 untranslated region of the gene for dystrophia myotonica-protein kinase (DMPK) .…”

Section: Homeobox Factorsmentioning

confidence: 99%

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: Intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage‐gated channels, methylation/acetylation, and transcription factors

Hermo

Pelletier

Cyr

et al. 2009

Microscopy Res & Technique

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As germ cells divide and differentiate from spermatogonia to spermatozoa, they share a number of structural and functional features that are common to all generations of germ cells and these features are discussed herein. Germ cells are linked to one another by large intercellular bridges which serve to move molecules and even large organelles from the cytoplasm of one cell to another. Mitochondria take on different shapes and features and topographical arrangements to accommodate their specific needs during spermatogenesis. The nuclear envelope and pore complex also undergo extensive modifications concomitant with the development of germ cell generations. Apoptosis is an event that is normally triggered by germ cells and involves many proteins. It occurs to limit the germ cell pool and acts as a quality control mechanism. The ubiquitin pathway comprises enzymes that ubiquitinate as well as deubiquitinate target proteins and this pathway is present and functional in germ cells. Germ cells express many proteins involved in water balance and pH control as well as voltage-gated ion channel movement. In the nucleus, proteins undergo epigenetic modifications which include methylation, acetylation, and phosphorylation, with each of these modifications signaling changes in chromatin structure. Germ cells contain specialized transcription complexes that coordinate the differentiation program of spermatogenesis, and there are many male germ cell-specific differences in the components of this machinery. All of the above features of germ cells will be discussed along with the specific proteins/genes and abnormalities to fertility related to each topic.

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“…Others tissues and organs that express DMPK mRNA include bone, testis, eye, skin, thymus, lung and liver. In contrast, no expression of DMPK transcript is found in ovary, pancreas and kidney O'Cochlain et al, 2004;Sarkar et al, 2004). The production of DMPK antibodies by using peptides or recombinant DMPK protein as immunogen has made possible the detection of DMPK at protein level (Lam et al, 2000;Pham et al, 1998;Ueda et al, 2000).…”

Section: Tissue Distribution Of Dmpkmentioning

confidence: 99%

“…In general, mRNA and DMPK protein expression appear strongly correlated. Highest levels of DMPK gene products are found in smooth muscle O'Cochlain et al, 2004;Sarkar et al, 2004), heart and skeletal muscle (Groenen et al, 2000;Lam et al, 2000;O'Cochlain et al, 2004;Sarkar et al, 2004). DMPK at protein level has also been identified in several brain regions (van der Ven et al, 1993) both in neurons and glia.…”

Section: Tissue Distribution Of Dmpkmentioning

confidence: 99%

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

Magaña¹,

Suárez-Sánchez²,

Leyva-García³

et al. 2012

Advances in Protein Kinases

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In situ hybridization analysis of Dmpk mRNA in adult mouse tissues

Cited by 36 publications

References 39 publications

Myotonic Dystrophy Protein Kinase Phosphorylates Phospholamban and Regulates Calcium Uptake in Cardiomyocyte Sarcoplasmic Reticulum

Myotonic Dystrophy Protein Kinase Phosphorylates Phospholamban and Regulates Calcium Uptake in Cardiomyocyte Sarcoplasmic Reticulum

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: Intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage‐gated channels, methylation/acetylation, and transcription factors

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

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