Repression of slow myosin heavy chain 2 gene expression in fast skeletal muscle fibers by muscarinic acetylcholine receptor and Gαq signaling

Jordan, Theresa; Li, Jinyuan; Jiang, Hongbin; DiMario, Joseph X.

doi:10.1083/jcb.200303164

Cited by 14 publications

(17 citation statements)

References 34 publications

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“…In contrast, innervated fast PM muscle fibers were resistant to slow MyHC2 gene expression. These results are in agreement with previously published data (DiMario and Stockdale, 1997;Jordan et al, 2003). However, innervated PM muscle fibers cultured in medium containing either 2-APB or xestospongin D did express the slow MyHC2 gene and immunostained with S58.…”

Section: Inhibition Of Ip3r Induces Slow Myhc2 Gene Expression In Innsupporting

confidence: 83%

“…IP3R1 activity regulates muscle fiber type greater in fast PM muscle fibers relative to slow MA muscle fibers and that innervation reduces PKC activities in both fiber types (DiMario, 2001;DiMario and Funk, 1999). However, PKC activity in innervated PM muscle fibers was still greater than in innervated MA muscle fibers (Jordan et al, 2003). As reduced PKC activity has been correlated with slow MyHC2 gene expression (above references), we hypothesized that PM muscle fibers, induced to express the slow MyHC2 gene by treatment with 2-APB, exhibited significantly less PKC activity.…”

Section: Inhibition Of Ip3r1 Activity Reduces Pkc Activitymentioning

confidence: 88%

“…Cell signaling initiated by muscarinic acetylcholine receptor activity and transduced via Gαq to phospholipase C activity repressed slow MyHC2 gene expression in innervated fast PM muscle fibers. Inhibition of the muscarinic acetylcholine receptor by atropine resulted in slow MyHC2 gene expression in PM muscle fibers, and constitutively active Gαq repressed slow MyHC2 gene expression in innervated MA muscle fibers (Jordan et al, 2003). Similarly, overexpression of wild-type PKCα repressed slow MyHC2 expression, whereas overexpression of a dominant-negative PKCα mutant induced slow MyHC2 gene expression in innervated PM muscle fibers (DiMario, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Regulation of skeletal muscle fiber type and slow myosin heavy chain 2 gene expression by inositol trisphosphate receptor 1

Jordan

Jiang

et al. 2005

Journal of Cell Science

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Innervation-dependent signaling cascades that control activation of downstream transcription factors regulate expression of skeletal muscle fiber type-specific genes. Many of the innervation-regulated signaling cascades in skeletal muscle are dependent on intracellular calcium and the mechanisms by which calcium is released from the sarcoplasmic reticulum (SR). We report that the inositol trisphosphate receptor 1 (IP3R1), responsible for calcium release from the SR as a slow wave, was more abundant in fast contracting compared to slow contracting avian muscle fibers. Furthermore, inhibition of IP3R1 activity by 2-aminoethoxydiphenylborate (2-APB) and xestospongin D induced a fiber type transition and expression of the slow myosin heavy chain 2 (slow MyHC2) gene in innervated fast muscle fibers. Activation of the slow MyHC2 promoter by IP3R1 inhibition was accompanied by a reduction in protein kinase C activity. In addition, inhibition of IP3R1 activity resulted in a reduction of nuclear factor of activated T cells (NFAT)-dependent transcription and nuclear localization, indicating that IP3R1 activity regulated NFAT transcription factor activity in skeletal muscle fibers. Myocyte enhancer factor 2 (MEF2)-dependent transcriptional activity was increased by innervation, but unaffected by IP3R1 activity. The results indicate that IP3R1 activity regulates muscle fiber type-specific gene expression in innervated muscle fibers.

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Section: Inhibition Of Ip3r Induces Slow Myhc2 Gene Expression In Innsupporting

confidence: 83%

Section: Inhibition Of Ip3r1 Activity Reduces Pkc Activitymentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of skeletal muscle fiber type and slow myosin heavy chain 2 gene expression by inositol trisphosphate receptor 1

Jordan

Jiang

et al. 2005

Journal of Cell Science

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“…The role of Wnt signaling in fiber type differentiation of mammalian fetal skeletal muscle remains unknown. Although the innervation-dependent extrinsic signals that determine fetal muscle fiber types have started to be uncovered (Jiang et al, 2004;Jordan et al, 2003Jordan et al, , 2005, the intrinsic and innervationindependent extrinsic factors that regulate initial fiber types of fetal muscle have not been identified.…”

Section: Discussionmentioning

confidence: 99%

Sox6 is required for normal fiber type differentiation of fetal skeletal muscle in mice

Hagiwara

Yeh

Liu

2007

Developmental Dynamics

141

138

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Sox6, a member of the Sox family of transcription factors, is highly expressed in skeletal muscle. Despite its abundant expression, the role of Sox6 in muscle development is not well understood. We hypothesize that, in fetal muscle, Sox6 functions as a repressor of slow fiber type-specific genes. In the wild-type mouse, differentiation of fast and slow fibers becomes apparent during late fetal stages (after approximately embryonic day 16). However, in the Sox6 null-p 100H mutant mouse, all fetal muscle fibers maintain slow fiber characteristics, as evidenced by expression of the slow myosin heavy chain MyHC-␤. Knockdown of Sox6 expression in wild-type myotubes results in a significant increase in MyHC-␤ expression, supporting our hypothesis. Analysis of the MyHC-␤ promoter revealed a Sox consensus sequence that likely functions as a negative cis-regulatory element. Together, our results suggest that Sox6 plays a critical role in the fiber type differentiation of fetal skeletal muscle.

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“…Release of acetylcholine from motor neurons at neuromuscular junctions is sufficient to activate vasodilation of muscle-associated arterioles via the muscarinic acetylcholine receptor (mAchR) as well as muscle fiber activity via the nicotinic acetylcholine receptor (nAchR) (Welsh and Segal, 1997). Inhibition of mAchR activity and associated signaling via Gαq in innervated fast muscle fibers is sufficient to induce slow MyHC2 gene expression (Jordan et al, 2003). Similarly, slow MyHC2 gene expression is induced in muscle fibers in which protein kinase C (PKC) activity is reduced (DiMario, 2001;DiMario and Funk, 1999).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of ryanodine receptor 1 in fast skeletal muscle fibers induces a fast-to-slow muscle fiber type transition

Jordan

Jiang

et al. 2004

Journal of Cell Science

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Skeletal muscle fiber type is regulated by innervation-induced cell signaling including calcium release mechanisms that lead to transcriptional activation of fiber type-specific genes. Avian fast pectoralis major (PM) and slow medial adductor (MA) muscles differentially control expression of the slow myosin heavy chain 2 (slow MyHC2) gene. We report here that slow MyHC2 gene expression in fast PM muscle fibers is repressed by endogenous activity of the ryanodine receptor 1 (RyR1). Inhibition of RyR1 with ryanodine led to expression of the slow MyHC2 gene in innervated PM muscle fibers in vitro. Administration of ryanodine to innervated PM muscle fibers also decreased protein kinase C (PKC) activity, the reduction of which is necessary for slow MyHC2 gene expression in both PM and MA muscle fibers. Furthermore, RyR1 inhibition increased slow MyHC2 promoter activity in innervated PM muscle fibers and enhanced transcriptional activities of nuclear factor of activated T cells (NFAT) and myocyte enhancer factor 2 (MEF2), as well as their interactions with their respective binding sites of the slow MyHC2 promoter. These results indicate that RyR1 activity in innervated fast PM muscle fibers contributes to the cell type-specific repression of slow muscle specific genes.

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Repression of slow myosin heavy chain 2 gene expression in fast skeletal muscle fibers by muscarinic acetylcholine receptor and Gαq signaling

Cited by 14 publications

References 34 publications

Regulation of skeletal muscle fiber type and slow myosin heavy chain 2 gene expression by inositol trisphosphate receptor 1

Regulation of skeletal muscle fiber type and slow myosin heavy chain 2 gene expression by inositol trisphosphate receptor 1

Sox6 is required for normal fiber type differentiation of fetal skeletal muscle in mice

Inhibition of ryanodine receptor 1 in fast skeletal muscle fibers induces a fast-to-slow muscle fiber type transition

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