CHRNA3 Membrane Protein Introduction

Introduction of CHRNA3

CHRNA3, also known as neuronal acetylcholine receptor subunit alpha-3 (NACHRA3), is a subunit in neuronal acetylcholine receptor (nAChRs) and is encoded by the CHRNA3 gene. nAChRs are ligand-gated ion channels activated by acetylcholine and nicotine, mediating synaptic transmission in brain and diverse functions in the periphery. nAChR is thought to be composed of different permutations of nine α subunits (α2–α10) and three β subunits (β2–β4) in humans. Some of these subunits form homopentameric receptors when expressed in heterologous expression systems (α7, α8 or α9), whereas other subunits assemble into heteropentameric structures with various combinations of α and β subunits. They form a dynamic structure which is able to adopt several conformational states responsible for different functional characteristics.

Function of CHRNA3 Membrane Protein

nAChRs assembled with different subunits may mediate different physiological functions. The α3-containing nAChRs subtype plays a pivotal role in regulating the inflammatory responses in endothelial cells and macrophages. In addition, several single nucleotide polymorphisms (SNPs) in NACHRA3 is identified to be associated with chronic obstructive pulmonary disease based on a Norwegian population. Moreover, both the CHRNA3 and CHRNA5 genes are expressed in areas of the human brain associated with addiction, such as the nucleus accumbens, amygdala and entorhinal cortex. The α3 and α5 subunits are obligate accessory subunits which cannot form functional nAChRs by themselves or in combination with only one other type of subunit. Moreover, the α3, α5 and β4 gene clusters are involved in the ethanol-induced stimulation and nicotine effects and play an important role in this process.

Fig.1 Schematic representation of an individual nAChR subunit protein. (Scofield. 2010)

Application of CHRNA3 Membrane Protein Literature

1. Criado M. Acetylcholine nicotinic receptor subtypes in chromaffin cells. Journal of Physiology. 2018, 470(1):13-20. PubMed ID:28791474
   
   

   This article reports that the α3, β4 and α5 subunits are clustered in genomes of different species, with the transcription factor Sp1 playing a coordinating role in the transcriptional regulation of these three subunits.

2. Kamens H.M., et al. The α3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation. Genes Brain Behav. 2009, 8(6):600-609. PubMed ID: 18826434
   
   

   This article describes that Chrna3 is a candidate gene for the acute locomotor stimulant response to ethanol that deserves further examination.

3. Joshi P.K., et al. Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan. Nature Communications. 2016, 7:11174. PubMed ID: 27029810
   
   

   This article suggests that common variants near the apolipoprotein E and CHRNA5 genes are associated with lifespan and a locus near CHRNA3/5 differentially affecting paternal lifespan.

4. Shmulewitz D., et al. CHRNA5/A3/B4 variant rs3743078 and nicotine-related phenotypes: indirect effects through nicotine craving. Journal of Studies on Alcohol & Drugs. 2016, 77(2):227-37. PubMed ID: 26997181
   
   

   This article suggests that CHRNA3, allele G of rs3743078 is associated with increased craving, CPD, and FTND scores and participants with several copies of the G allele smoke more cigarettes.

5. Yang C., et.al. Role of α3-containing nicotinic acetylcholine receptors subtypes in vascular inflammation. British Journal of Pharmacology. 2016, 173(22):3235-3247. PubMed ID: 27572927
   
   

   This article indicates that α3-nAChRs play a pivotal role in regulating the inflammatory responses in endothelial cells and macrophages and the mechanisms involve the modulations of multiple cell signaling pathways.

CHRNA3 Preparation Options

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Reference

1. Scofield M D. (2010). Elucidating the transcriptional network underlying expression of a neuronal nicotinic receptor gene: a dissertation. University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 497.

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