CHRNG Membrane Protein Introduction

Introduction of CHRNG

CHRNG, also known as acetylcholine receptor subunit gamma (ACHRG), encoded by the CHRNG gene, is one of the subunits of the acetylcholine receptor (AChR). CHRNG gene is located on chromosome 1, spans 6.5 kb, and contains 12 exons and 11 introns in the mouse. Mammalian muscle nicotinic acetylcholine receptor (AChR) consists of four membrane-spanning subunits and its composition differs between embryonic and adult muscles. In embryonic muscles, it includes two α, one β, one δ, and one γ subunit; the γ subunit is later replaced by the ε-subunit during postnatal development. This unique temporal expression pattern of γ-subunit suggests it may play specific roles in embryonic muscles. In the absence of a γ-subunit, the combination of α, β and δ subunits can be assembled into a functional receptor in vivo.

Function of CHRNG Membrane Protein

Typically, the γ subunit is expressed during the embryonic and neonatal phases and is replaced by the ε-subunit during the first 2 weeks after birth. The physiological role of this transformation is unclear, but there is evidence that the γ subunit and the ε subunit both plays a specific role in the embryonic and adult neuromuscular junction, respectively. In addition, the γ-subunit in embryonic helps to establish the primary encounter of muscle and axon. Thus, the γ subunit not only contributes to neuromuscular signal transduction but also plays an important role in neuromuscular organogenesis. Impaired γ-subunit structure leads to abnormal AChR function in fetal life with reduced prenatal muscle strength and movement. Moreover, the γ-subunit may be involved in interacting with rapsyn, a cytoplasmic protein required for receptor clustering. What’s more, the γ-subunit mutation prevents the correct localization of fetal AChR in the human embryonic kidney cell membranes, and the expression pattern in prenatal mice corresponds to the human clinical phenotype. In conclusion, γ-subunit of muscle nicotinic AChR plays an important role in neuromuscular development, neuromuscular signal transduction, neuromuscular organogenesis, ligand binding, and insertion of receptors in the membrane.

Fig.1 Structure and subunit composition of fetal AChR in muscle cells. (Hoffmann, 2006)

Application of CHRNG Membrane Protein Literature

1. Mongeon R., et al. An acetylcholine receptor lacking both γ and ε subunits mediates transmission in zebrafish slow muscle synapses. Journal of General Physiology. 2011, 138(3):353-66. PubMed ID:21844221.
   
   

   This article suggests muscle synaptic function is first attributed to receptor isoforms consisting of only three distinct subunits and the unique functional features provided by the α(2)βδ(2) receptor may play a central role in mediating the sustained contractile characteristics of this muscle type.

2. Hoffmann K., et al. Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal γ subunit. American Journal of Human Genetics. 2006, 79(2):303-312. PubMed ID: 16826520.
   
   

   This article concludes that Escobar syndrome is an inherited fetal myasthenic disease that also affects neuromuscular organogenesis.

3. Liu Y., et al. Essential roles of the acetylcholine receptor gamma-subunit in neuromuscular synaptic patterning. Development. 2008, 135(11):1957-67. PubMed ID: 18434415.
   
   

   This article demonstrates that the gamma-subunit is shown to be essential for the formation of pre-patterned AChR clusters, which in turn plays an important role in determining subsequent patterns of neuromuscular synapse development.

4. Yun L., et al. Postsynaptic development of the neuromuscular junction in mice lacking the γ-subunit of muscle nicotinic acetylcholine receptor. Journal of Molecular Neuroscience. 2010, 40(1-2):21-6. PubMed ID: 19672725.
   
   

   This article suggests that functional AChRs are present in mutant muscle membranes and in the absence of a gamma-subunit, and the combination of α, β, and δ subunits can be assembled into a functional receptor in vivo.

5. Azim S., et al. Alternatively spliced variants of gamma-subunit of muscle-type acetylcholine receptor in fetal and adult skeletal muscle of mouse. Cellular and Molecular Neurobiology. 2012, 32(6):957-963. PubMed ID: 22488527.
   
   

   This article reveals three transcriptional variants of the γ-subunit of the nicotinic AChR and their similarities and differences.

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Reference

1. Hoffmann K, et al. (2006). Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal γ subunit. American Journal of Human Genetics. 79(2), 303-312.

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