CHRNE Membrane Protein Introduction

Introduction of CHRNE

CHRNE, also known as acetylcholine receptor subunit epsilon (ACHRE), is one of the subunits of the acetylcholine receptor (AChR) and is encoded by the CHRNE gene in humans. The mammalian ChR is a pentameric transmembrane ion channel composed of 2α, 1β, 1δ and 1ε or 1γ subunit. Upon innervation, fetal form of AChR containing the γ subunit is replaced by adult form containing ε subunit. The muscle-type AChRs are located at the endplate of neuromuscular junctions (NMJ) where they mediate neuromuscular transmission, whereas the neuronal-type receptors are found throughout the peripheral and central nervous system. Neuronal-type subunits are expressed in multiple tissues, including vertebrate adult skeletal muscle, digestive system, lungs, keratinocytes, endothelial cells, and lymphocytes, while the muscle-type 1 receptor subunit is expressed in chick ciliary ganglia.

Basic Information of CHRNE
Protein Name	Acetylcholine receptor subunit epsilon
Gene Name	CHRNE
Aliases	ACHRE
Organism	Homo sapiens (Human)
UniProt ID	Q04844
Transmembrane Times	4
Length (aa)	493
Sequence	MARAPLGVLLLLGLLGRGVGKNEELRLYHHLFNNYDPGSRPVREPEDTVTISLKVTLTNLISLNEKEETLTTSVWIGIDWQDYRLNYSKDDFGGIETLRVPSELVWLPEIVLENNIDGQFGVAYDANVLVYEGGSVTWLPPAIYRSVCAVEVTYFPFDWQNCSLIFRSQTYNAEEVEFTFAVDNDGKTINKIDIDTEAYTENGEWAIDFCPGVIRRHHGGATDGPGETDVIYSLIIRRKPLFYVINIIVPCVLISGLVLLAYFLPAQAGGQKCTVSINVLLAQTVFLFLIAQKIPETSLSVPLLGRFLIFVMVVATLIVMNCVIVLNVSQRTPTTHAMSPRLRHVLLELLPRLLGSPPPPEAPRAASPPRRASSVGLLLRAEELILKKPRSELVFEGQRHRQGTWTAAFCQSLGAAAPEVRCCVDAVNFVAESTRDQEATGEEVSDWVRMGNALDNICFWAALVLFSVGSSLIFLGAYFNRVPDLPYAPCIQP

Function of CHRNE Membrane Protein

Replacement of the γ subunit in the embryonic AChR by ε subunit in the adult form is essential for maintenance of functional neuromuscular synapses in adult muscles, and leads to a greater channel conductance to Na⁺, K⁺ and Ca²⁺ than in fetal receptors. The expression of γ and ε subunits of the AChR from mammalian skeletal muscle is regulated independently during myogenic differentiation and innervation. Furthermore, the AChR ε subunit is expressed in thymocytes and thus may promote the production of AChR-reactive T cells in the early stages of maturation. The mutations in AChR ε subunit may lead to myasthenia gravis syndrome in individuals with the appropriate immunogenetic background. Mice lacking the ε-subunit die in early stages of life due to the lack of endplate AChR, suggesting ε subunit is essential for maintaining NMJ function.

CHRNE Membrane Protein Introduction Fig.1 Structure and subunit composition of adult AChR in muscle cells. (Hoffmann, 2006)

Application of CHRNE Membrane Protein Literature

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 that for the first time, muscle synaptic function can be ascribed to a receptor isoform that is composed of only three different subunits and the unique functional features offered by the α(2)βδ(2) receptor likely play a central role in mediating the persistent contractions characteristic to this muscle type.
Owens J., et al. Contributions of the gamma and epsilon subunit family to nicotinic acetylcholine receptor function. Receptors & Channels. 1993, 1(2):173-80. PubMed ID: 8081721.

This article suggests that AChRs formed in combination with a Torpedo gamma subunit have a significantly lower conductance than those containing a mouse epsilon subunit.
Wu X., et al. Ocular myasthenia gravis induced by human acetylcholine receptor ε subunit immunization in HLA DR3 transgenic mice. Immunology Letters. 2015, 168(2):306-12. PubMed ID: 26493475

This article reveals that the interaction between the HLA class II allele and the AChR subunit may have a profound effect on the clinical course of myasthenia gravis.
Lazaridis K., et al. Characterization of a reproducible rat EAMG model induced with various human acetylcholine receptor domains. Journal of Neuroimmunology. 2017, 303:13-21. PubMed ID: 28038891

This article shows that extracellular domain (ECD) of the human AChR subunit (α, β, γ, δ, and ε) expressed in yeast produces a strong antigenic response in Lewis rats, and the pathogenicity is significantly different.

CHRNE Preparation Option

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CHRNE antibody development services.

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are very honored to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

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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