CHRNA7 Membrane Protein Introduction

Introduction of CHRNA7

The α7 neuronal nicotinic acetylcholine receptor (α7nAChR) encoded by CHRNA7 gene, is a member of the nicotinic acetylcholine receptor family. The AChR is ligand-gated ion channel of five subunits, stimulated endogenously by acetylcholine, resulting in flux of the cations Na⁺, K⁺, and Ca²⁺. Eleven nicotinic receptor subunit genes are expressed in the human brain, including α2-7, 9, 10, and β2-4, which form multiple pentameric heteromers and a homomeric receptor, usually with only α7 subunits. Each subunit is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region.

Basic Information of CHRNA7
Protein Name	Neuronal acetylcholine receptor subunit alpha-7
Gene Name	CHRNA7
Aliases	NACHRA7
Organism	Homo sapiens (Human)
UniProt ID	P36544
Transmembrane Times	4
Length (aa)	502
Sequence	MRCSPGGVWLALAASLLHVSLQGEFQRKLYKELVKNYNPLERPVANDSQPLTVYFSLSLLQIMDVDEKNQVLTTNIWLQMSWTDHYLQWNVSEYPGVKTVRFPDGQIWKPDILLYNSADERFDATFHTNVLVNSSGHCQYLPPGIFKSSCYIDVRWFPFDVQHCKLKFGSWSYGGWSLDLQMQEADISGYIPNGEWDLVGIPGKRSERFYECCKEPYPDVTFTVTMRRRTLYYGLNLLIPCVLISALALLVFLLPADSGEKISLGITVLLSLTVFMLLVAEIMPATSDSVPLIAQYFASTMIIVGLSVVVTVIVLQYHHHDPDGGKMPKWTRVILLNWCAWFLRMKRPGEDKVRPACQHKQRRCSLASVEMSAVAPPPASNGNLLYIGFRGLDGVHCVPTPDSGVVCGRMACSPTHDEHLLHGGQPPEGDPDLAKILEEVRYIANRFRCQDESEAVCSEWKFAACVVDRLCLMAFSVFTIICTIGILMSAPNFVEAVSKDFA

Function of CHRNA7 Membrane Protein

The CHRNA7 gene cluster is ubiquitously expressed in the human body and has roles in CNS and peripheral development, cognitive performance, and inflammation. It has been revealed that the dysfunction of α7nAChR is associated with mental and degenerative diseases. Besides, the early appearance of α7nAChR in evolution as an important source of calcium entry into the cell may explain its residual peripheral functions and development of synaptic roles. The CHRNA7 gene is the parent of other nicotinic receptors, and of a recent additional duplication to form the new gene, CHRFAM7A, only found in humans. Once this receptor binds acetylcholine, it undergoes an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Fig.1 Postulated mechanism for the interaction between CHRNA7 polymorphisms, APOE ε4 and smoking. (Weng, 2016)

Application of CHRNA7 Membrane Protein in Literature

Weng P., et al. CHRNA7 polymorphisms and response to cholinesterase inhibitors in Alzheimer's disease. PLos One. 2013, 8(12):e84059. PubMed ID: 24391883

This article finds a significant correlation between better ChEI response and CHRNA7 polymorphisms.
Hamoud N., et al. Effect of genetic polymorphisms (SNPs) in CHRNA7 gene on response to acetylcholinesterase inhibitors (AChEI) in patients with Alzheimer's disease. Current Drug Targets. 2017, 18(10):1179-1190. PubMed ID: 26424395

This article suggests that galantamine (AChEI) and donepezil (DP) induce upregulation of α7nAChR protein levels, which protect neurons from degeneration.
Braga I.L., et al. Effect of APOE and CHRNA7 genotypes on the cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2015, 30(2):139-44. PubMed ID: 24951635

This article reports that the SNP rs6494223 of CHRNA7, as well as APOE∊4, could be helpful for understanding the response to ChEI treatment in patients with Alzheimer's disease.
Gillentine M.A., et al. Functional consequences of CHRNA7 copy-number alterations in induced pluripotent stem cells and neural progenitor cells. The American Journal of Human Genetics. 2017, 101(6):874-887. PubMed ID: 29129316

This article reveals that α7 nAChR-dependent calcium signal cascades are down-regulated in both 15q13.3 deletion and duplication NPCs.
Fei R., et al. α7 nicotinic acetylcholine receptor in tumor-associated macrophages inhibits colorectal cancer metastasis through the JAK2/STAT3 signaling pathway. Oncology Reports. 2017, 38(5):2619-2628. PubMed ID: 28901507

This article suggests that CHRNA7 expressed in TAMs in human CRC patients plays a significant role in preventing metastasis and could be a prognostic marker in CRCs which may be regulated by the JAK2/STAT3 signaling pathway.

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Reference

Weng P H, et al. (2016). CHRNA7 polymorphisms and dementia risk: interactions with apolipoprotein ε4 and cigarette smoking. Scientific Reports. 6:27231.

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