Control of myogenic factor genes by the membrane depolarization/protein kinase C cascade in chick skeletal muscle

C F Huang1, C M Neville, J Schmidt

  • 1Department of Biochemistry and Cell Biology, State University of New York, Stony Brook 11794.

FEBS Letters
|March 15, 1993
PubMed

Insights

Electrical stimulation differentially affects myogenic factor genes in chick skeletal muscle. Myogenin gene activity rapidly declines, suggesting a key role in acetylcholine receptor gene activation during denervation.

Area of Science:

  • Muscle physiology
  • Molecular biology
  • Neuroscience

Background:

  • Denervation of skeletal muscle leads to significant changes in gene expression.
  • Acetylcholine receptor (AChR) gene expression is rapidly downregulated following denervation.
  • Myogenic factor genes play crucial roles in muscle development and maintenance.

Purpose of the Study:

  • To investigate the differential response of myogenic factor genes to electrical stimulation in denervated chick skeletal muscle.
  • To elucidate the role of myogenin in the regulation of AChR gene activity during denervation supersensitivity.
  • To examine the involvement of Protein Kinase C (PKC) signaling in these processes.

Main Methods:

  • Electrical stimulation of denervated chick skeletal muscle.
  • Quantitative analysis of myogenic factor gene activity (myogenin, MyoD, myf5, herculin).
  • Pharmacological manipulation using PKC activator (PMA) and kinase inhibitor (staurosporine).

Main Results:

  • Myogenin gene activity declined rapidly (t1/2 ≈ 2 min) post-denervation, mirroring AChR gene inactivation.
  • Other myogenic bHLH genes (MyoD, myf5, herculin) showed slower or no decline in activity.
  • PKC activation rapidly blocked myogenin transcription; electrical stimulation's effect was abolished by PKC inhibition or depletion.

Conclusions:

  • Myogenin exhibits a unique, rapid response to denervation, distinct from other myogenic factors.
  • Myogenin plays a specialized role in activating AChR genes during denervation supersensitivity.
  • PKC signaling is critical for the rapid inactivation of myogenin gene transcription following denervation.

Related Concept Videos

Cross-bridge Cycle01:26

Cross-bridge Cycle

As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
Formation of Muscle Fibers from Myoblasts01:13

Formation of Muscle Fibers from Myoblasts

De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Smooth Muscle Contraction01:25

Smooth Muscle Contraction

Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...