CHRNE

Template:Short description Template:Cs1 config An Error has occurred retrieving Wikidata item for infobox Acetylcholine receptor subunit epsilon is a protein that in humans is encoded by the CHRNE gene.

Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome.

Role in health and disease

Congenital myasthenic syndrome (CMS) is associated with genetic defects that affect proteins of the neuromuscular junction. Postsynaptic defects are the most frequent cause of CMS and often result in abnormalities in the acetylcholine receptor (AChR). The majority of mutations causing CMS are found in the AChR subunits genes.

Out of all mutations associated with CMS, more than half are mutations in one of the four genes encoding the adult AChR subunits. Mutations of the AChR often result in endplate deficiency. The most common AChR gene mutation that underlies CMS is the mutation of the CHRNE gene. The CHRNE gene codes for the epsilon subunit of the AChR. Most mutations are autosomal recessive loss-of-function mutations and as a result there is endplate AChR deficiency. CHRNE is associated with changing the kinetic properties of the AChR. One type of mutation of the epsilon subunit of the AChR introduces an arginine (Arg) into the binding site at the α/ε subunit interface of the receptor. The addition of a cationic Arg into the anionic environment of the AChR binding site greatly reduces the kinetic properties of the receptor. The result of the newly introduced ARG is a 30-fold reduction of agonist affinity, 75-fold reduction of gating efficiency, and an extremely weakened channel opening probability. This type of mutation results in an extremely fatal form of CMS.

See also

• Nicotinic acetylcholine receptor

Further reading

• Hantaï D, Richard P, Koenig J, Eymard B (October 2004). "Congenital myasthenic syndromes". Current Opinion in Neurology. 17 (5): 539–551. doi:10.1097/00019052-200410000-00004. PMID 15367858. S2CID 45357882.
• Yu XM, Hall ZW (July 1991). "Extracellular domains mediating epsilon subunit interactions of muscle acetylcholine receptor". Nature. 352 (6330): 64–67. Bibcode:1991Natur.352...64Y. doi:10.1038/352064a0. PMID 1712080. S2CID 4245374.
• Ohno K, Hutchinson DO, Milone M, Brengman JM, Bouzat C, Sine SM, et al. (January 1995). "Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunit". Proceedings of the National Academy of Sciences of the United States of America. 92 (3): 758–762. doi:10.1073/pnas.92.3.758. PMC 42699. PMID 7531341.
• Gomez CM, Gammack JT (May 1995). "A leucine-to-phenylalanine substitution in the acetylcholine receptor ion channel in a family with the slow-channel syndrome". Neurology. 45 (5): 982–985. doi:10.1212/wnl.45.5.982. PMID 7538206. S2CID 35877992.
• Lobos EA (September 1993). "Five subunit genes of the human muscle nicotinic acetylcholine receptor are mapped to two linkage groups on chromosomes 2 and 17". Genomics. 17 (3): 642–650. doi:10.1006/geno.1993.1384. PMID 7902325.
• Brenner HR, Rotzler S, Kues WA, Witzemann V, Sakmann B (October 1994). "Nerve-dependent induction of AChR epsilon-subunit gene expression in muscle is independent of state of differentiation". Developmental Biology. 165 (2): 527–536. doi:10.1006/dbio.1994.1272. PMID 7958418.
• Uchitel O, Engel AG, Walls TJ, Nagel A, Atassi MZ, Bril V (December 1993). "Congenital myasthenic syndromes: II. Syndrome attributed to abnormal interaction of acetylcholine with its receptor". Muscle & Nerve. 16 (12): 1293–1301. doi:10.1002/mus.880161205. PMID 8232384. S2CID 26474245.
• Ohno K, Wang HL, Milone M, Bren N, Brengman JM, Nakano S, et al. (July 1996). "Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit". Neuron. 17 (1): 157–170. doi:10.1016/S0896-6273(00)80289-5. PMID 8755487. S2CID 17773515.
• Engel AG, Ohno K, Milone M, Wang HL, Nakano S, Bouzat C, et al. (September 1996). "New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome". Human Molecular Genetics. 5 (9): 1217–1227. doi:10.1093/hmg/5.9.1217. PMID 8872460.
• Engel AG, Ohno K, Bouzat C, Sine SM, Griggs RC (November 1996). "End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit". Annals of Neurology. 40 (5): 810–817. doi:10.1002/ana.410400521. PMID 8957026. S2CID 83884178.
• Ohno K, Quiram PA, Milone M, Wang HL, Harper MC, Pruitt JN, et al. (May 1997). "Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations". Human Molecular Genetics. 6 (5): 753–766. doi:10.1093/hmg/6.5.753. PMID 9158150.
• Nichols P, Croxen R, Vincent A, Rutter R, Hutchinson M, Newsom-Davis J, et al. (April 1999). "Mutation of the acetylcholine receptor epsilon-subunit promoter in congenital myasthenic syndrome". Annals of Neurology. 45 (4): 439–443. doi:10.1002/1531-8249(199904)45:4<439::AID-ANA4>3.0.CO;2-W. PMID 10211467. S2CID 83632162.
• Croxen R, Newland C, Betty M, Vincent A, Newsom-Davis J, Beeson D (October 1999). "Novel functional epsilon-subunit polypeptide generated by a single nucleotide deletion in acetylcholine receptor deficiency congenital myasthenic syndrome". Annals of Neurology. 46 (4): 639–647. doi:10.1002/1531-8249(199910)46:4<639::AID-ANA13>3.0.CO;2-1. PMID 10514102. S2CID 85150509.
• Abicht A, Stucka R, Karcagi V, Herczegfalvi A, Horváth R, Mortier W, et al. (October 1999). "A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin". Neurology. 53 (7): 1564–1569. doi:10.1212/wnl.53.7.1564. PMID 10534268.
• Kindler CH, Verotta D, Gray AT, Gropper MA, Yost CS (March 2000). "Additive inhibition of nicotinic acetylcholine receptors by corticosteroids and the neuromuscular blocking drug vecuronium". Anesthesiology. 92 (3): 821–832. doi:10.1097/00000542-200003000-00026. PMID 10719961. S2CID 27038179.
• Wang HL, Ohno K, Milone M, Brengman JM, Evoli A, Batocchi AP, et al. (September 2000). "Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome". The Journal of General Physiology. 116 (3): 449–462. doi:10.1085/jgp.116.3.449. PMC 2233692. PMID 10962020.
• Sieb JP, Kraner S, Rauch M, Steinlein OK (August 2000). "Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations". Human Genetics. 107 (2): 160–164. doi:10.1007/s004390000359. PMID 11030414. S2CID 22171041.
• Dan I, Watanabe NM, Kajikawa E, Ishida T, Pandey A, Kusumi A (July 2002). "Overlapping of MINK and CHRNE gene loci in the course of mammalian evolution". Nucleic Acids Research. 30 (13): 2906–2910. doi:10.1093/nar/gkf407. PMC 117062. PMID 12087176.

External links

• CHRNE+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Template:UCSC gene info

This article incorporates text from the United States National Library of Medicine, which is in the public domain.