Muscle Cell News Volume 1.07 | Apr 25 2016

Splicing Misregulation of SCN5A Contributes to Cardiac-Conduction Delay and Heart Arrhythmia in Myotonic Dystrophy
Researchers identified novel splicing alterations in myotonic dystrophy heart samples, including a switch from adult exon 6B towards fetal exon 6A in the cardiac sodium channel, SCN5A. Importantly, reproducing splicing alteration of Scn5a in mice is sufficient to promote heart arrhythmia and cardiac-conduction delay, two predominant features of myotonic dystrophy. [Nat Commun] Full Article | Press Release

Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses
The authors describe an approach that combines features of engineered heart muscle and cardiospheres: Micro-Heart Muscle arrays, in which elongated muscle fibers are formed in an easily fabricated template, with as few as 2,000 iPS-derived cardiomyocytes per individual tissue. [Sci Rep] Full Article | Press Release | Video

Autophagy Inhibition of hsa-miR-19a-3p/19b-3p by Targeting TGF-β R II during TGF-β1-Induced Fibrogenesis in Human Cardiac Fibroblasts
Scientists determined the role of MiR-19a-3p/19b-3p in regulating autophagy-mediated fibrosis of human cardiac fibroblasts. Transforming growth factor-β1 (TGF-β1) promotes collagen I α2 and fibronectin synthesis in human cardiac fibroblasts and that is paralleled by autophagic activation in these cells. [Sci Rep] Full Article

Central Role for GSK3β in the Pathogenesis of Arrhythmogenic Cardiomyopathy
Investigators showed that SB216763 (SB2) prevents myocyte injury and cardiac dysfunction in vivo in two murine models of arrhythmogenic cardiomyopathy at baseline and in response to exercise. SB2-treated mice with desmosome mutations showed improvements in ventricular ectopy and myocardial fibrosis/inflammation as compared with vehicle-treated mice. [JCI Insight] Full Article | Press Release

SKELETAL MUSCLE CELLS

Laminopathies Disrupt Epigenomic Developmental Programs and Cell Fate
Investigators fused mutated forms of the lamin A protein to bacterial DNA adenine methyltransferase (Dam) to define euchromatic-heterochromatin (epigenomic) transitions at the nuclear envelope during myogenesis. [Sci Transl Med] Abstract | Press Release

Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy
Scientists present an analytical workflow based upon the principles of protein correlation profiling that enabled them to model the molecular composition of the dystrophin-glycoprotein complex in mouse skeletal muscle. [Mol Cell Proteomics] Abstract | Full Article

SMOOTH MUSCLE CELLS

Epithelium-Generated Neuropeptide Y Induces Smooth Muscle Contraction to Promote Airway Hyperresponsiveness
Researchers determined that neuropeptide Y promotes airway hyperresponsiveness through the induction of Rho kinase activity and phosphorylation of myosin light chain, which induces airway smooth muscle contraction. [J Clin Invest] Full Article | Press Release 1 | Press Release 2

The Molecular Basis of the Genesis of Basal Tone in Internal Anal Sphincter
Investigators showed that deletion of myosin light-chain kinases in the smooth muscle cells from internal anal sphincter (IAS-SMCs) abolishes basal tone, impairing defecation. Pharmacological regulation of ryanodine receptors, L-type voltage-dependent Ca²⁺ channels or TMEM16A Ca²⁺-activated Cl⁻ channels significantly changes global cytosolic Ca²⁺ concentration and the tone. [Nat Commun] Full Article | Press Release

Neutrophil-Derived Exosomes: A New Mechanism Contributing to Airway Smooth Muscle Remodeling
Scientists determined whether bioactive exosomes are released by neutrophils, and characterized their proteomic profile, and evaluated their capacity to modulate airway smooth muscle cell proliferation. [Am J Respir Cell Mol Biol] Abstract

Epithelial Splicing Regulatory Protein 1 (ESRP1) Is a New Regulator of Stomach Smooth Muscle Development and Plasticity
Researchers identified the RNA-binding protein ESRP1 as an early marker of developing and undifferentiated stomach mesenchyme. Using a gain-of-function approach, they found that in chicken embryos, sustained expression of ESRP1 impairs stomach smooth muscle cell differentiation and FGFR2 splicing profile. [Dev Biol] Abstract

Skeletal Muscle as a Gene Regulatory Endocrine Organ
Skeletal muscle is gaining increased attention as an endocrine organ. Recently, novel myokines and new effects of already established myokines have been identified. Scientists give an update on the recent advances in the field. [Curr Opin Clin Nutr Metab Care] Abstract

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REPRIEVE, Largest HIV-Related Cardiovascular Disease Clinical Trial Ever, Enrolls More Than 1,000 Participants
The trial is designed to investigate among people living with HIV whether statin use can prevent a very common comorbidity – cardiovascular disease. To date, the clinical trial has enrolled nearly 1,200 participants living with HIV across approximately 85 trial sites. [Massachusetts General Hospital] Press Release

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NEW PhD Positions – Molecular and Cellular Biology (IGBMC)

NEW Research Technician – Myogenesis, Neurogenesis and Related Diseases (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Immuno-Metabolic Modulation of Skeletal Muscle Insulin Sensitivity (Karolinska Institutet)

PhD Position – Muscle Fiber Type Switch in Congenital Myopathies (King’s College London)

Postdoctoral Fellow – Pathogenesis of Heart and Vascular Injury (University of Alberta)

Research Associate – Muscle Molecular Biology and Biochemistry (The University of York)

Postdoctoral Researcher – Stem Cell Biology Regenerative Medicine (NUI Galway)

Research Assistant – Skeletal Muscle Cell Biology (Nestlé)

Postdoctoral Positions – Tissue Repair/Inflammation (Institut Pasteur)

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