A new look at thin filament regulation in vertebrate skeletal muscle

Squire, John M.; Morris, Edward P.

doi:10.1096/fasebj.12.10.761

Cited by 195 publications

(133 citation statements)

References 76 publications

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“…Binding of Ca 21 to TnC leads to a sequence of conformational changes in the overall Tn complex that is ultimately conferred to tropomyosin and releases the inhibition of the interaction between myosin and actin, thereby allowing contraction to occur (see reviews 3,4,[6][7][8]13 ).…”

Section: Skeletal and Cardiac Isoforms Of Troponinmentioning

confidence: 99%

“…Contraction and relaxation in striated muscle is accomplished by the action of the complex assembly of proteins that form thick and thin filaments that slide past each other to shorten and lengthen muscle sarcomeres (see Figure 1) (see reviews in Refs. [3][4][5][6][7][8][9]. The major constituent of the thin filament is actin, a 42-kDa globular protein that self-associates to form a double helical structure that has associated with it the accessory proteins troponin (Tn) and tropomyosin (Tm).…”

Section: Introductionmentioning

confidence: 99%

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Invited review: Probing the structures of muscle regulatory proteins using small‐angle solution scattering

Jeffries

Trewhella

2011

Biopolymers

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Small‐angle X‐ray and neutron scattering with contrast variation have made important contributions in advancing our understanding of muscle regulatory protein structures in the context of the dynamic molecular processes governing muscle action. The contributions of the scattering investigations have depended upon the results of key crystallographic, NMR, and electron microscopy experiments that have provided detailed structural information that has aided in the interpretation of the scattering data. This review will cover the advances made using small‐angle scattering techniques, in combination with the results from these complementary techniques, in probing the structures of troponin and myosin binding protein C. A focus of the troponin work has been to understand the isoform differences between the skeletal and cardiac isoforms of this major calcium receptor in muscle. In the case of myosin binding protein C, significant data are accumulating, indicating that this protein may act to modulate the primary calcium signals from troponin, and interest in its biological role has grown because of linkages between gene mutations in the cardiac isoform and serious heart disease. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 505–516, 2011.

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Section: Skeletal and Cardiac Isoforms Of Troponinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Invited review: Probing the structures of muscle regulatory proteins using small‐angle solution scattering

Jeffries

Trewhella

2011

Biopolymers

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“…In muscles, troponin I (TnI) is a key element in the protein complex that regulates sliding of thin over thick filaments (Farah and Reinach, 1995;Geeves and Lehrer, 1998;Squire and Morris, 1998;Maytum et al, 2003). Several TnI protein isoforms are generated, either from transcription of independent genes (e.g., vertebrates) or from differential splicing of a single gene primary transcript (e.g., Drosophila).…”

Section: Introductionmentioning

confidence: 99%

Transcription ofDrosophilaTroponin I Gene Is Regulated by Two Conserved, Functionally Identical, Synergistic Elements

Marín

Toledo-Rodriguez

Ferrús

2004

MBoC

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The Drosophila wings-up A gene encodes Troponin I. Two regions, located upstream of the transcription initiation site (upstream regulatory element) and in the first intron (intron regulatory element), regulate gene expression in specific developmental and muscle type domains. Based on LacZ reporter expression in transgenic lines, upstream regulatory element and intron regulatory element yield identical expression patterns. Both elements are required for full expression levels in vivo as indicated by quantitative reverse transcription-polymerase chain reaction assays. Three myocyte enhancer factor-2 binding sites have been functionally characterized in each regulatory element. Using exon specific probes, we show that transvection is based on transcriptional changes in the homologous chromosome and that Zeste and Suppressor of Zeste 3 gene products act as repressors for wings-up A. Critical regions for transvection and for Zeste effects are defined near the transcription initiation site. After in silico analysis in insects (Anopheles and Drosophila pseudoobscura) and vertebrates (Ratus and Coturnix), the regulatory organization of Drosophila seems to be conserved. Troponin I (TnI) is expressed before muscle progenitors begin to fuse, and sarcomere morphogenesis is affected by TnI depletion as Z discs fail to form, revealing a novel developmental role for the protein or its transcripts. Also, abnormal stoichiometry among TnI isoforms, rather than their absolute levels, seems to cause the functional muscle defects. INTRODUCTIONContractile protein systems are widely represented in most cell types as a force generator device (Davison et al., 2000). In muscles, troponin I (TnI) is a key element in the protein complex that regulates sliding of thin over thick filaments (Farah and Reinach, 1995;Geeves and Lehrer, 1998;Squire and Morris, 1998;Maytum et al., 2003). Several TnI protein isoforms are generated, either from transcription of independent genes (e.g., vertebrates) or from differential splicing of a single gene primary transcript (e.g., Drosophila). Amino acid substitutions in constitutive or alternatively spliced exons in TnI can lead to pathological conditions such as familial hypertrophic cardiomyopathy (Carrier et al., 1993;Coonar and McKenna, 1997) and distal arthrogryposis (Sung et al., 2003), due to abnormal interactions with other sarcomere components. Also, TnI is a relevant indicator of heart failure (Lewinter and Vanburen, 2002) and a potent angiogenesis inhibitor through its interaction with polycystin-2 (Li et al., 2003). The potential applications that this knowledge could provide, however, are handicapped by the scant information on the regulatory mechanisms of TnI gene expression. This issue is particularly relevant in the context of future gene therapy strategies and justifies this in vivo study of the regulatory mechanism of the Drosophila homologue. In addition, this study takes advantage of the fact that TnI in Drosophila is encoded by a single gene, wings up A (wupA), and that isoform replacem...

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“…Contraction of skeletal muscles is achieved via the influx of Ca 2 þ into the cytosol and its interaction with Troponin C, triggering the ATP-dependent sliding of a-actin and myosin filaments along each other. For relaxation, Ca 2 þ is actively removed from the cytosol into the sarcoplasmic reticulum by Serca proteins, which are ATP-dependent Ca 2 þ -specific ion pumps 5,6 .…”

mentioning

confidence: 99%

Ebf factors and MyoD cooperate to regulate muscle relaxation via Atp2a1

et al. 2014

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Myogenic regulatory factors such as MyoD and Myf5 lie at the core of vertebrate muscle differentiation. However, E-boxes, the cognate binding sites for these transcription factors, are not restricted to the promoters/enhancers of muscle cell-specific genes. Thus, the specificity in myogenic transcription is poorly defined. Here we describe the transcription factor Ebf3 as a new determinant of muscle cell-specific transcription. In the absence of Ebf3 the lung does not unfold at birth, resulting in respiratory failure and perinatal death. This is due to a hypercontractile diaphragm with impaired Ca 2 þ efflux-related muscle functions. Expression of the Ca 2 þ pump Serca1 (Atp2a1) is downregulated in the absence of Ebf3, and its transgenic expression rescues this phenotype. Ebf3 binds directly to the promoter of Atp2a1 and synergises with MyoD in the induction of Atp2a1. In skeletal muscle, the homologous family member Ebf1 is strongly expressed and together with MyoD induces Atp2a1. Thus, Ebf3 is a new regulator of terminal muscle differentiation in the diaphragm, and Ebf factors cooperate with MyoD in the induction of muscle-specific genes.

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A new look at thin filament regulation in vertebrate skeletal muscle

Cited by 195 publications

References 76 publications

Invited review: Probing the structures of muscle regulatory proteins using small‐angle solution scattering

Invited review: Probing the structures of muscle regulatory proteins using small‐angle solution scattering

Transcription ofDrosophilaTroponin I Gene Is Regulated by Two Conserved, Functionally Identical, Synergistic Elements

Ebf factors and MyoD cooperate to regulate muscle relaxation via Atp2a1

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