Getting Folded: Chaperone Proteins in Muscle Development, Maintenance and Disease

Smith, Daniel A.; Carland, Carmen Rivero; Guo, Yanjuan; Bernstein, Sanford I.

doi:10.1002/ar.22980

Cited by 34 publications

(33 citation statements)

References 145 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The physiological function of chaperone and co-chaperone in muscle cell development remains elusive [38, 39]. In order to further understand the role of Tid1, a mitochondrial co-chaperone, on mediating myogenesis, we determined the expression of Tid1 during the induced differentiation of myoblasts (C2C12 cells) in vitro.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis

Cheng¹,

Hung²,

Lee

et al. 2016

Stem Cell Res Ther

View full text Add to dashboard Cite

BackgroundTid1 is a mitochondrial co-chaperone protein and its transcript is abundantly expressed in skeletal muscle tissues. However, the physiological function of Tid1 during skeletal myogenesis remains unclear.MethodsIn vitro induced differentiation assay of mouse myoblast C2C12 cells was applied to examine the physiological role of Tid1 during skeletal myogenesis. In addition, transgenic mice with muscle specific (HSA-Cre) Tid1 deletion were established and examined to determine the physiological function of Tid1 during skeletal muscle development in vivo.ResultsExpression of Tid1 protein was upregulated in the differentiated C2C12 cells, and the HSA-Tid1f/f mice displayed muscular dystrophic phenotype. The expression of myosin heavy chain (MyHC), the protein served as the muscular development marker, was reduced in HSA-Tid1f/f mice at postnatal day (P)5 and P8. The protein levels of ATP sensor (p-AMPK) and mitochondrial biogenesis protein (PGC-1α) were also significantly reduced in HSA-Tid1f/f mice. Moreover, Tid1 deficiency induced apoptotic marker Caspase-3 in muscle tissues of HSA-Tid1f/f mice. Consistent with the in vivo finding, we observed that downregulation of Tid1 not only reduced the ATP production but also abolished the differentiation ability of C2C12 cells by impairing the mitochondrial activity.ConclusionTogether, our results suggest that Tid1 deficiency reduces ATP production and abolishes mitochondrial activity, resulting in energy imbalance and promoting apoptosis of muscle cells during myogenesis. It will be of importance to understand the function of Tid1 during human muscular dystrophy in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0443-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis

Cheng¹,

Hung²,

Lee

et al. 2016

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…Which are the key regions in UNC-45B mediating its myosin-chaperoning and actin gliding inhibiting functions? Based on the crystal structures and biochemical data on Drosophila [6,13,14], Caenorhabditis elegans [15][16][17] UNC-45B and also based on the molecular dynamics and biophysical studies on human UNC-45B [5,18,19], we hypothesize that the UCS domain independently interacts with the myosin head, prevents thermal aggregation, and maintains mechanically unfolded intermediates of the myosin head competent for refolding, underscoring its interaction with non-native states. In contrast, the central domain is capable of binding to native myosin heads but unable to prevent misfolding [5].…”

mentioning

confidence: 96%

mentioning

confidence: 99%

The central domain of UNC‐45 chaperone inhibits the myosin power stroke

et al. 2017

View full text Add to dashboard Cite

The multidomain UNC‐45B chaperone is crucial for the proper folding and function of sarcomeric myosin. We recently found that UNC‐45B inhibits the translocation of actin by myosin. The main functions of the UCS and TPR domains are known but the role of the central domain remains obscure. Here, we show—using in vitro myosin motility and ATPase assays—that the central domain alone acts as an inhibitor of the myosin power stroke through a mechanism that allows ATP turnover. Hence, UNC‐45B is a unique chaperone in which the TPR domain recruits Hsp90; the UCS domain possesses chaperone‐like activities; and the central domain interacts with myosin and inhibits the actin translocation function of myosin. We hypothesize that the inhibitory function plays a critical role during the assembly of myofibrils under stress and during the sarcomere development process.

show abstract

“…Heat shock proteins (HSP) are a family of molecular chaperones which assist in protein folding and remodeling, and are rapidly upregulated in response to cellular stressors. HSP90 is strongly implicated in thick filament organization (Smith, Carland, Guo, & Bernstein, 2014), with mutations or disrupted chaperone activity causing the disassembly of thick filaments in myofibrils (Du, Li, Bian, & Zhong, 2008;He, Liu, Tian, & Du, 2015). We investigated the effects of HSP90 on myosin substitution in thick filaments.…”

Section: Modulation Of the Myosin Replacement Rate By Myosin Chapermentioning

confidence: 99%

Myosin: Formation and maintenance of thick filaments

Ojima

2019

Animal Science Journal

View full text Add to dashboard Cite

Skeletal muscle consists of bundles of myofibers containing millions of myofibrils, each of which is formed of longitudinally aligned sarcomere structures. Sarcomeres are the minimum contractile unit, which mainly consists of four components: Z‐bands, thin filaments, thick filaments, and connectin/titin. The size and shape of the sarcomere component is strictly controlled. Surprisingly, skeletal muscle cells not only synthesize a series of myofibrillar proteins but also regulate the assembly of those proteins into the sarcomere structures. However, authentic sarcomere structures cannot be reconstituted by combining purified myofibrillar proteins in vitro, therefore there must be an elaborate mechanism ensuring the correct formation of myofibril structure in skeletal muscle cells. This review discusses the role of myosin, a main component of the thick filament, in thick filament formation and the dynamics of myosin in skeletal muscle cells. Changes in the number of myofibrils in myofibers can cause muscle hypertrophy or atrophy. Therefore, it is important to understand the fundamental mechanisms by which myofibers control myofibril formation at the molecular level to develop approaches that effectively enhance muscle growth in animals.

show abstract

Getting Folded: Chaperone Proteins in Muscle Development, Maintenance and Disease

Cited by 34 publications

References 145 publications

Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis

Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis

The central domain of UNC‐45 chaperone inhibits the myosin power stroke

Myosin: Formation and maintenance of thick filaments

Contact Info

Product

Resources

About