A novel mutation in the DNM2 gene impairs dynamin 2 localization in skeletal muscle of a patient with late onset centronuclear myopathy

Kierdaszuk, Biruta; Berdyński, Mariusz; Karolczak, Justyna; Redowicz, Maria Jolanta; Żekanowski, Cezary; Kamińska, Anna

doi:10.1016/j.nmd.2012.12.007

Cited by 25 publications

(23 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These larger oligomers localize at the plasma membrane as well as in the cytoplasm 36 . Abnormal cytosolic accumulation of dynamin-2 has been also observed in myofibers from CNM patients carrying a PH-domain mutation 65 and in fibers isolated from HTZ mice 11 . We also observed large intracellular inclusions in myoblasts expressing R369W, R465W or R522H mutants (Fig.…”

Section: Discussionmentioning

confidence: 90%

Dynamin-2 mutations linked to Centronuclear Myopathy impair actin-dependent trafficking in muscle cells

González‐Jamett

Báez‐Matus

Olivares

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Dynamin-2 is a ubiquitously expressed GTP-ase that mediates membrane remodeling. Recent findings indicate that dynamin-2 also regulates actin dynamics. Mutations in dynamin-2 cause dominant centronuclear myopathy (CNM), a congenital myopathy characterized by progressive weakness and atrophy of skeletal muscles. However, the muscle-specific roles of dynamin-2 affected by these mutations remain elusive. Here we show that, in muscle cells, the GTP-ase activity of dynamin-2 is involved in de novo actin polymerization as well as in actin-mediated trafficking of the glucose transporter GLUT4. Expression of dynamin-2 constructs carrying CNM-linked mutations disrupted the formation of new actin filaments as well as the stimulus-induced translocation of GLUT4 to the plasma membrane. Similarly, mature muscle fibers isolated from heterozygous knock-in mice that harbor the dynamin-2 mutation p.R465W, an animal model of CNM, exhibited altered actin organization, reduced actin polymerization and impaired insulin-induced translocation of GLUT4 to the sarcolemma. Moreover, GLUT4 displayed aberrant perinuclear accumulation in biopsies from CNM patients carrying dynamin-2 mutations, further suggesting trafficking defects. These results suggest that dynamin-2 is a key regulator of actin dynamics and GLUT4 trafficking in muscle cells. Our findings also support a model in which impairment of actin-dependent trafficking contributes to the pathological mechanism in dynamin-2-associated CNM.

show abstract

Section: Discussionmentioning

confidence: 90%

Dynamin-2 mutations linked to Centronuclear Myopathy impair actin-dependent trafficking in muscle cells

González‐Jamett

Báez‐Matus

Olivares

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…We have recently shown that a point mutation within the pleckstrin‐homology domain of the dynamin 2 gene led to centronuclear myopathy, characterized by a central localization of the muscle nuclei and demonstrated that dynamin 2, MVI, clathrin (endocytosis marker) and TGN 46 (trans Golgi cisternae marker) co‐localized on the surface of those aberrant nuclei (Kierdaszuk et al, ). MVI was also present within the nuclei (Fig.…”

Section: Resultsmentioning

confidence: 99%

Myosin VI Localization and Expression in Striated Muscle Pathology

Karolczak

Weis²,

Ehler

et al. 2014

The Anatomical Record

Self Cite

View full text Add to dashboard Cite

Myosin VI (MVI) is a unique unconventional myosin translocating, unlike other myosins, towards the minus end of actin filaments. It is involved in numerous cellular processes such as endocytosis, intracellular trafficking, cell migration, and transcription. In mammalian skeletal muscles it localizes mainly to sarcoplasmic reticulum and is also present within the muscle nuclei and at the neuromuscular junction (Karolczak et al. Histochem Cell Biol 2013; 23:219-228). We have also shown that in denervated rat hindlimb muscle the MVI expression level is significantly increased and its localization is changed, indicating an important role of MVI in striated muscle pathology. Here, we addressed this problem by examining the distribution and expression levels of myosin VI in biopsies of skeletal muscles from patients with different myopathies. We found that, particularly in myopathies associated with fiber atrophy, the amount of MVI was enhanced and its localization in affected fibers was changed. Also, since a mutation within the human MVI gene was shown to be associated with cardiomyopathy, we assessed MVI localization and expression level in cardiac muscle using wild type and MLP(2/2) mice, a dilated cardiomyopathy model. No significant difference in MVI expression level was observed for both types of animals. MVI was found at intercalated discs and also at the sarcoplasmic reticulum. In the knockout mice, it was also present in ring-like structures surrounding the nuclei. The data indicate that in striated muscle MVI could be engaged in sarcoplasmic reticulum maintenance and/or functioning, vesicular transport, signal transmission and possibly in gene transcription.

show abstract

“…Dynamin 2 is required for muscle development and its mutation causes centronuclear myopathy in skeletal muscle [16]. The dynamin 3 locus encodes an antisense transcript, Dnm3os, which gives rise to miR-199a-2 and another microRNA, miR-214.…”

Section: Introductionmentioning

confidence: 99%

MiRNA-199a-3p Regulates C2C12 Myoblast Differentiation through IGF-1/AKT/mTOR Signal Pathway

Long

et al. 2013

IJMS

View full text Add to dashboard Cite

MicroRNAs constitute a class of ~22-nucleotide non-coding RNAs. They modulate gene expression by associating with the 3′ untranslated regions (3′ UTRs) of messenger RNAs (mRNAs). Although multiple miRNAs are known to be regulated during myoblast differentiation, their individual roles in muscle development are still not fully understood. In this study, we showed that miR-199a-3p was highly expressed in skeletal muscle and was induced during C2C12 myoblasts differentiation. We also identified and confirmed several genes of the IGF-1/AKT/mTOR signal pathway, including IGF-1, mTOR, and RPS6KA6, as important cellular targets of miR-199a-3p in myoblasts. Overexpression of miR-199a-3p partially blocked C2C12 myoblast differentiation and the activation of AKT/mTOR signal pathway, while interference of miR-199a-3p by antisense oligonucleotides promoted C2C12 differentiation and myotube hypertrophy. Thus, our studies have established miR-199a-3p as a potential regulator of myogenesis through the suppression of IGF-1/AKT/mTOR signal pathway.

show abstract

A novel mutation in the DNM2 gene impairs dynamin 2 localization in skeletal muscle of a patient with late onset centronuclear myopathy

Cited by 25 publications

References 35 publications

Dynamin-2 mutations linked to Centronuclear Myopathy impair actin-dependent trafficking in muscle cells

Dynamin-2 mutations linked to Centronuclear Myopathy impair actin-dependent trafficking in muscle cells

Myosin VI Localization and Expression in Striated Muscle Pathology

MiRNA-199a-3p Regulates C2C12 Myoblast Differentiation through IGF-1/AKT/mTOR Signal Pathway

Contact Info

Product

Resources

About