scholarly journals The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles

2021 ◽  
Author(s):  
Robbert J. van der Pijl ◽  
Andrea A. Domenighetti ◽  
Farah Sheikh ◽  
Elisabeth Ehler ◽  
Coen A. C. Ottenheijm ◽  
...  
Keyword(s):  
Thin Filament ◽  
Muscle Growth ◽  
Muscle Mechanics ◽  
Muscle Physiology ◽  
Striated Muscles ◽  
Associated Proteins ◽  
Αb Crystallin ◽  
Health And Disease ◽  
Passive Muscle ◽  
Cardiac Intercalated Disc

AbstractMuscle specific signaling has been shown to originate from myofilaments and their associated cellular structures, including the sarcomeres, costameres or the cardiac intercalated disc. Two signaling hubs that play important biomechanical roles for cardiac and/or skeletal muscle physiology are the N2B and N2A regions in the giant protein titin. Prominent proteins associated with these regions in titin are chaperones Hsp90 and αB-crystallin, members of the four-and-a-half LIM (FHL) and muscle ankyrin repeat protein (Ankrd) families, as well as thin filament-associated proteins, such as myopalladin. This review highlights biological roles and properties of the titin N2B and N2A regions in health and disease. Special emphasis is placed on functions of Ankrd and FHL proteins as mechanosensors that modulate muscle-specific signaling and muscle growth. This region of the sarcomere also emerged as a hotspot for the modulation of passive muscle mechanics through altered titin phosphorylation and splicing, as well as tethering mechanisms that link titin to the thin filament system.

Dynamic localization of αB-crystallin at the microtubule cytoskeleton network in beating heart cells

2020 ◽  
Vol 168 (2) ◽  
pp. 125-137 ◽  
Author(s):  
Eri Ohto-Fujita ◽  
Saaya Hayasaki ◽  
Aya Atomi ◽  
Soichiro Fujiki ◽  
Toshiyuki Watanabe ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Resonance Energy Transfer ◽  
Focal Adhesions ◽  
Resonance Energy ◽  
Heart Cells ◽  
Striated Muscles ◽  
Slow Skeletal Muscle ◽  
Αb Crystallin ◽  
Cardiac Muscles ◽  
Myoblast Cells

Abstract αB-crystallin is highly expressed in the heart and slow skeletal muscle; however, the roles of αB-crystallin in the muscle are obscure. Previously, we showed that αB-crystallin localizes at the sarcomere Z-bands, corresponding to the focal adhesions of cultured cells. In myoblast cells, αB-crystallin completely colocalizes with microtubules and maintains cell shape and adhesion. In this study, we show that in beating cardiomyocytes α-tubulin and αB-crystallin colocalize at the I- and Z-bands of the myocardium, where it may function as a molecular chaperone for tubulin/microtubules. Fluorescence recovery after photobleaching (FRAP) analysis revealed that the striated patterns of GFP-αB-crystallin fluorescence recovered quickly at 37°C. FRAP mobility assay also showed αB-crystallin to be associated with nocodazole-treated free tubulin dimers but not with taxol-treated microtubules. The interaction of αB-crystallin and free tubulin was further confirmed by immunoprecipitation and microtubule sedimentation assay in the presence of 1–100 μM calcium, which destabilizes microtubules. Förster resonance energy transfer analysis showed that αB-crystallin and tubulin were at 1–10 nm apart from each other in the presence of colchicine. These results suggested that αB-crystallin may play an essential role in microtubule dynamics by maintaining free tubulin in striated muscles, such as the soleus or cardiac muscles.

Altered expression of thin filament-associated proteins in hypertrophied urinary bladder smooth muscle

2005 ◽  
Vol 25 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Anita S. Mannikarottu ◽  
Michael E. DiSanto ◽  
Stephen A. Zderic ◽  
Alan J. Wein ◽  
Samuel Chacko
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Thin Filament ◽  
Bladder Smooth Muscle ◽  
Altered Expression ◽  
Associated Proteins ◽  
Urinary Bladder Smooth Muscle

scholarly journals Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

2010 ◽  
Vol 189 (1) ◽  
pp. 95-109 ◽  
Author(s):  
David S. Gokhin ◽  
Raymond A. Lewis ◽  
Caroline R. McKeown ◽  
Roberta B. Nowak ◽  
Nancy E. Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thin Filament ◽  
Striated Muscle ◽  
Fiber Type ◽  
Actin Dynamics ◽  
Muscle Physiology ◽  
Skeletal Muscle Function ◽  
Capping Proteins ◽  
Locomotor Deficits ◽  
End Capping

During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore the effects of deleting Tmod1 from skeletal muscle. Myofibril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1. Tmod4 localizes to thin filament pointed ends in Tmod1-null embryonic muscle, whereas both Tmod3 and -4 localize to pointed ends in Tmod1-null adult muscle. Substitution by Tmod3 and -4 occurs despite their weaker interactions with striated muscle tropomyosins. However, the absence of Tmod1 results in depressed isometric stress production during muscle contraction, systemic locomotor deficits, and a shift to a faster fiber type distribution. Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology.

Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

2010 ◽  
Vol 135 (5) ◽  
pp. i4-i4
Author(s):  
David S. Gokhin ◽  
Raymond A. Lewis ◽  
Caroline R. McKeown ◽  
Roberta B. Nowak ◽  
Nancy E. Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thin Filament ◽  
Muscle Physiology ◽  
End Capping ◽  
Pointed End

Expression of the dystrophin-glycoprotein complex is a marker for human airway smooth muscle phenotype maturation

2008 ◽  
Vol 294 (1) ◽  
pp. L57-L68 ◽  
Author(s):  
Pawan Sharma ◽  
Thai Tran ◽  
Gerald L. Stelmack ◽  
Karol McNeill ◽  
Reinoud Gosens ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Serum Deprivation ◽  
Muscle Physiology ◽  
Smooth Muscle Tissue ◽  
Glycoprotein Complex ◽  
Contractile Phenotype ◽  
Dystrophin Glycoprotein Complex ◽  
Health And Disease ◽  
Dystrophin Glycoprotein

Airway smooth muscle (ASM) cells may contribute to asthma pathogenesis through their capacity to switch between a synthetic/proliferative and a contractile phenotype. The multimeric dystrophin-glycoprotein complex (DGC) spans the sarcolemma, linking the actin cytoskeleton and extracellular matrix. The DGC is expressed in smooth muscle tissue, but its functional role is not fully established. We tested whether contractile phenotype maturation of human ASM is associated with accumulation of DGC proteins. We compared subconfluent, serum-fed cultures and confluent cultures subjected to serum deprivation, which express a contractile phenotype. Western blotting confirmed that β-dystroglycan, β-, δ-, and ε-sarcoglycan, and dystrophin abundance increased six- to eightfold in association with smooth muscle myosin heavy chain (smMHC) and calponin accumulation during 4-day serum deprivation. Immunocytochemistry showed that the accumulation of DGC subunits was specifically localized to a subset of cells that exhibit robust staining for smMHC. Laminin competing peptide (YIGSR, 1 μM) and phosphatidylinositol 3-kinase (PI3K) inhibitors (20 μM LY-294002 or 100 nM wortmannin) abrogated the accumulation of smMHC, calponin, and DGC proteins. These studies demonstrate that the accumulation of DGC is an integral feature for phenotype maturation of human ASM cells. This provides a strong rationale for future studies investigating the role of the DGC in ASM smooth muscle physiology in health and disease.

Effect of Oxidative Stress on the Expression of Thin Filament-Associated Proteins in Gastric Smooth Muscle Cells

2014 ◽  
Vol 70 (1) ◽  
pp. 225-231 ◽  
Author(s):  
Othman Abdullah Al-Shboul ◽  
Ayman Mustafa ◽  
Mukhallad Mohammad ◽  
Mustafa Al-Shehabat ◽  
Asmaa Yousef ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Thin Filament ◽  
Muscle Cells ◽  
Gastric Smooth Muscle ◽  
Associated Proteins
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