Phosphorylation of the regulatory light chain of myosin in striated muscle: methodological perspectives

Yu, Hongwei; Chakravorty, Samya; Song, Weihua; Ferenczi, Michael A.

doi:10.1007/s00249-016-1128-z

Cited by 35 publications

(40 citation statements)

References 204 publications

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“…Myosin molecules are tightly associated with different myosin light chains, modulating the stability of the myosin head, contributing to force production, and altering the association with the actomyosin network [45,46]. The regulatory isoforms MYL2 and MLC2F are phosphorylated at S14 and S15, and these modifications are associated with force potentiation in fast skeletal muscles [47,48].…”

Section: Phosphoproteomics Reveals Distinct Kinase Activities Betweenmentioning

confidence: 99%

High-throughput proteomics fiber typing (ProFiT) for comprehensive characterization of single skeletal muscle fibers

et al. 2020

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Background: Skeletal muscles are composed of a heterogeneous collection of fiber types with different physiological adaption in response to a stimulus and disease-related conditions. Each fiber has a specific molecular expression of myosin heavy chain molecules (MyHC). So far, MyHCs are currently the best marker proteins for characterization of individual fiber types, and several proteome profiling studies have helped to dissect the molecular signature of whole muscles and individual fibers. Methods: Herein, we describe a mass spectrometric workflow to measure skeletal muscle fiber type-specific proteomes. To bypass the limited quantities of protein in single fibers, we developed a Proteomics high-throughput fiber typing (ProFiT) approach enabling profiling of MyHC in single fibers. Aliquots of protein extracts from separated muscle fibers were subjected to capillary LC-MS gradients to profile MyHC isoforms in a 96-well format. Muscle fibers with the same MyHC protein expression were pooled and subjected to proteomic, pulsed-SILAC, and phosphoproteomic analysis. Results: Our fiber type-specific quantitative proteome analysis confirmed the distribution of fiber types in the soleus muscle, substantiates metabolic adaptions in oxidative and glycolytic fibers, and highlighted significant differences between the proteomes of type IIb fibers from different muscle groups, including a differential expression of desmin and actinin-3. A detailed map of the Lys-6 incorporation rates in muscle fibers showed an increased turnover of slow fibers compared to fast fibers. In addition, labeling of mitochondrial respiratory chain complexes revealed a broad range of Lys-6 incorporation rates, depending on the localization of the subunits within distinct complexes. Conclusion: Overall, the ProFiT approach provides a versatile tool to rapidly characterize muscle fibers and obtain fiberspecific proteomes for different muscle groups.

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Section: Phosphoproteomics Reveals Distinct Kinase Activities Betweenmentioning

confidence: 99%

High-throughput proteomics fiber typing (ProFiT) for comprehensive characterization of single skeletal muscle fibers

et al. 2020

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“…Activation of the muscle not only involves the canonical movement of tropomyosin on the thin filament to expose binding sites for myosin heads but also additionally requires myosin heads to be released from their shutdown state (Irving 2017 ). It is likely that phosphorylation of the regulatory light chains (RLCs) plays a role in this in both cardiac and skeletal muscles (Yu et al 2016 ), through affecting the stability of the shutdown state.…”

Section: Myosin Structure—a Brief Overviewmentioning

confidence: 99%

Disease mutations in striated muscle myosins

Parker

Peckham

2020

Biophys Rev

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Over 1000 disease-causing missense mutations have been found in human β-cardiac, α-cardiac, embryonic and adult fast myosin 2a myosin heavy chains. Most of these are found in human β-cardiac myosin heavy chain. Mutations in β-cardiac myosin cause hypertrophic cardiomyopathy predominantly, whereas those in α-cardiac are associated with many types of heart disease, of which the most common is dilated cardiomyopathy. Mutations in embryonic and fast myosin 2a affect skeletal muscle function. This review provides a short overview of the mutations in the different myosin isoforms and their disease-causing effects. Keywords β-Cardiac myosin. α-Cardiac myosin. Embryonic myosin. Cardiac disease. Skeletal muscle disease. Missense mutation Abbreviations FHC Familial hypertrophic cardiomyopathy HCM Hypertrophic cardiomyopathy DCM Dilated cardiomyopathy LDM Laing distal myopathy MSM Myosin storage myopathy S1 Subfragment-1 (myosin motor domain) S2 Subfragment-2 LMM Light meromyosin (myosin tail) RLC Regulatory light chain ELC Essential light chain

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“…The effects of phosphorylation of RLC MYL2 at Ser15 by the cardiac and skeletal myosin light chain kinases (MLCK) have been extensively examined (89, 126, 624). Accordingly, it was demonstrated that it renders the lever arm of MyHC stiffer, potentiates isometric and concentric force production, and increases myofilament Ca 2+ sensitivity in both cardiac and skeletal muscles, reviewed in (514, 573, 574, 618). Consistent with these findings, constitutive expression of phosphomimetic Myl2 (i.e., Ser15Asp) in myocardia prevented the development of HCM in transgenic mice carrying the HCM-linked Asp166Val MYL2 missense mutation (620).…”

Section: Myosinmentioning

confidence: 99%

Thick Filament Protein Network, Functions, and Disease Association

Wang

Geist

Grogan

et al. 2018

Comprehensive Physiology

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Sarcomeres consist of highly ordered arrays of thick myosin and thin actin filaments along with accessory proteins. Thick filaments occupy the center of sarcomeres where they partially overlap with thin filaments. The sliding of thick filaments past thin filaments is a highly regulated process that occurs in an ATP-dependent manner driving muscle contraction. In addition to myosin that makes up the backbone of the thick filament, four other proteins which are intimately bound to the thick filament, myosin binding protein-C, titin, myomesin, and obscurin play important structural and regulatory roles. Consistent with this, mutations in the respective genes have been associated with idiopathic and congenital forms of skeletal and cardiac myopathies. In this review, we aim to summarize our current knowledge on the molecular structure, subcellular localization, interacting partners, function, modulation via posttranslational modifications, and disease involvement of these five major proteins that comprise the thick filament of striated muscle cells. © 2018 American Physiological Society. Compr Physiol 8:631-709, 2018.

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Phosphorylation of the regulatory light chain of myosin in striated muscle: methodological perspectives

Cited by 35 publications

References 204 publications

High-throughput proteomics fiber typing (ProFiT) for comprehensive characterization of single skeletal muscle fibers

High-throughput proteomics fiber typing (ProFiT) for comprehensive characterization of single skeletal muscle fibers

Disease mutations in striated muscle myosins

Thick Filament Protein Network, Functions, and Disease Association

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