Neuronal control of myogenic regulatory factor accumulation in fetal muscle

Washabaugh, Charles H.; Ontell, Martin P.; Shand, Stuart H.; Bradbury, Neil A.; Kant, Jeffrey A.; Ontell, Marcia

doi:10.1002/dvdy.21078

Cited by 11 publications

(12 citation statements)

References 54 publications

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“…Muscle fiber size is controlled, in part, by muscle use. Because defects in synaptic transmission can lead to a decrease in muscle activity and myofiber size (35,36), we studied the arrangement and organization of neuromuscular synapses in dKO mice. We evaluated neuromuscular synapses by examining the distribution of motor axons and synapses in diaphragm muscles from embryonic day 18.5 (E18.5) mice.…”

Section: Resultsmentioning

confidence: 99%

Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro

Joseph

Lü

Radu

et al. 2017

Molecular and Cellular Biology

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Skeletal myogenesis is regulated by signal transduction, but the factors and mechanisms involved are not well understood. The group I Paks Pak1 and Pak2 are related protein kinases and direct effectors of Cdc42 and Rac1. Group I Paks are ubiquitously expressed and specifically required for myoblast fusion in Drosophila. We report that both Pak1 and Pak2 are activated during mammalian myoblast differentiation. One pathway of activation is initiated by N-cadherin ligation and involves the cadherin coreceptor Cdo with its downstream effector, Cdc42. Individual genetic deletion of Pak1 and Pak2 in mice has no overt effect on skeletal muscle development or regeneration. However, combined muscle-specific deletion of Pak1 and Pak2 results in reduced muscle mass and a higher proportion of myofibers with a smaller cross-sectional area. This phenotype is exacerbated after repair to acute injury. Furthermore, primary myoblasts lacking Pak1 and Pak2 display delayed expression of myogenic differentiation markers and myotube formation. These results identify Pak1 and Pak2 as redundant regulators of myoblast differentiation in vitro and in vivo and as components of the promyogenic Ncad/Cdo/Cdc42 signaling pathway.KEYWORDS Pak, cell adhesion, cell differentiation, myogenesis, regeneration, signal transduction C ell differentiation is a complex process whereby precursor cells take on tissuespecific structure and function. Lineage-restricted transcription factors lie at the heart of cell differentiation, but the process is often initiated and fortified by ubiquitous signaling pathways that function in many biological contexts. Skeletal myogenesis serves as a paradigm for cell differentiation. Differentiation of skeletal myoblasts is a coordinated process involving adoption of a cell-type-specific transcriptional program and morphological changes, including fusion into multinucleated myofibers (1, 2). MyoD family proteins (MyoD, Myf5, myogenin, and MRF4) are muscle-specific transcription factors that act in concert with other, more broadly expressed transcription factors to establish the muscle phenotype (1, 3). The activities of these factors are regulated posttranslationally by non-muscle-specific signal transduction pathways. One such pathway is the p38␣/␤ mitogen-activated protein kinase (MAPK; here simply p38) pathway (4). p38 is activated during myogenic differentiation in vitro, and its inhibition results in impaired differentiation (5-7). Furthermore, mice lacking p38␣ exhibit delayed myofiber growth and maturation (8).The signals that initiate p38 activity during myoblast differentiation are poorly understood. One mechanism is via activation of a signaling complex nucleated at sites of cadherin-based cell-cell adhesion (9, 10). The transmembrane IgSF coreceptor Cdo (also called Cdon) is bound in cis to N-cadherin (Ncad) in myoblasts. During myoblast differentiation, or acutely upon Ncad ligation, the Cdo intracellular region associates directly with (i) Bnip-2, a scaffold protein for Cdc42, and (ii) JLP, a scaffo...

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Section: Resultsmentioning

confidence: 99%

Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro

Joseph

Lü

Radu

et al. 2017

Molecular and Cellular Biology

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“…Cytosolic and membrane fractioning were performed as described [26–28]. Briefly, TA muscles were homogenized using a handheld Tissue Tearor ™ in ice-cold buffer A (20 mM sodium pyrophosphate, 20 mM sodium phosphate monobasic, 1 mM MgCl2, 0.5 mM EDTA, 303 mM sucrose with a complete protease inhibitor cocktail [Roche Diagnostics, Indianapolis, IN]).…”

Section: Methodsmentioning

confidence: 99%

Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle

Zhang

Taylor

Yang

et al. 2015

Experimental Cell Research

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The voltage-gated calcium channel (Cav) β1a subunit (Cavβ1a) plays an important role in excitation-contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Cavβ1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160-244 aa) and Cavβ1a NH2-terminus (1-99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Cavβ1a/YFP shows that TnT3 facilitates Cavβ1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation.

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“…Moreover, the expression pattern of some muscle-specific genes is dependent on innervation (449,450). For example, expression of AChR subunit genes and of distinct myosin isoforms that specify the contractile properties of the muscle (slow versus fast twitch) is strongly influenced by the pattern of impulse activity delivered by the nerve (388).…”

Section: A Development Of Skeletal Musclementioning

confidence: 99%

Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting

Tintignac

Brenner

Rüegg

2015

Physiological Reviews

332

341

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The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia.

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Neuronal control of myogenic regulatory factor accumulation in fetal muscle

Cited by 11 publications

References 54 publications

Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro

Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro

Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle

Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting

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