The E protein CTF4 and acetylcholine receptor expression in development and denervation supersensitivity
C M Neville1, Y H Choe, Y S Lee
1Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129-2060, USA.
The Journal of Biological Chemistry
|June 5, 1998
Summary
Skeletal muscle denervation reactivates acetylcholine receptor gene expression, involving the transcription factor CTF4 (chicken homologue of human HTF4/HEB) and myogenin. This myogenin/CTF4 heterodimer is crucial for restoring gene transcription after nerve loss.
Area of Science:
- Molecular Biology
- Neuroscience
- Muscle Physiology
Background:
- Motor activity suppresses extrasynaptic gene expression in skeletal muscle.
- Denervation triggers gene re-expression, mirroring developmental patterns, particularly for acetylcholine receptors.
Purpose of the Study:
- Identify trans-acting factors regulating acetylcholine receptor alpha-subunit gene expression in denervated muscle.
- Investigate the role of CTF4 and myogenin in skeletal muscle gene transcription.
Main Methods:
- Screening for DNA-binding factors in the acetylcholine receptor enhancer region.
- Analyzing CTF4 gene expression patterns during muscle development and maturation.
- Using antisense expression vectors to assess the in vivo function of myogenin, CTF4, and E12 in denervated muscle.
Main Results:
- CTF4, a homolog of human HTF4/HEB, was identified as a factor binding the acetylcholine receptor alpha-subunit enhancer.
- CTF4 expression parallels myogenin and acetylcholine receptor expression in developing muscle.
- Myogenin and CTF4, but not MyoD or E12, antisense vectors significantly impaired denervation-induced reporter gene activation.
Conclusions:
- A myogenin/CTF4 heterodimer is implicated in regulating acetylcholine receptor gene expression in vivo.
- CTF4 plays a key role in the transcriptional response to denervation in skeletal muscle.
Related Concept Videos
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:23Cholinergic Neurons: Neurotransmission
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
01:25Cholinergic Receptors: Muscarinic
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
01:15Cholinergic Receptors: Nicotinic
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
01:29Neuromuscular Junction And Blockade
The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...