Introduction of CHRNA5
CHRNA5, also known as neuronal acetylcholine receptor subunit alpha-5 (NACHRA5), is a protein that in humans is encoded by the CHRNA5 gene. The neuronal acetylcholine receptors (nAChRs) are divided into several subtypes that are formed through varying combinations of homologous subunits arranged around a central channel. So far, 12 subunits have been identified in mammals and designated as either α-type (α2-α10) or β-type (β2-β4) based on their homology to the muscle α1 subunit. Each nAChR subunit has four conserved transmembrane (TM) regions and a cytoplasmic loop of variable length and sequence. α5 subunit is an accessory subunit that forms pentamers with either α4β2, α3β4, or α3β2 subunits, and together, these constitute 10-37% of all nAChRs. Although high levels of expression are found only in few brain areas, CHRNA5 mRNA has been found in the majority of brain regions, suggesting that α5 nAChRs could have a substantial impact on brain function.
|Basic Information of CHRNA5|
|Protein Name||Neuronal acetylcholine receptor subunit alpha-5|
|Organism||Homo sapiens (Human)|
Function of CHRNA5 Membrane Protein
The majority of functional neuronal nAChRs are composed of two α and three β subunits, with “duplex” (α/β) or “triplex” combinations (αxαyβ or αβxβy). The α5 subunit is involved in nAChR receptors with αxαyβ combinations but cannot yield functional receptors when expressed alone or in combination with β subunits only. Although the α5 subunit is not necessary for the assembly of functional receptors, they can alter the pharmacological and biophysical properties of nAChR, and these effects depend on the nature of the subunit co-expressed with α5. When co-expressed with α3 and α2, α5 increases sensitivity to ACh, but this effect is not observed when α2 is replaced by α4. In contrast, the presence of α5 increases the calcium permeability and desensitization rate in nAChRs containing α3β2 and α3β4. In the peripheral nervous system, α5 is found in the sympathetic and parasympathetic ganglia where the nAChRs containing α5 may affect the autonomic control of several organ systems. In the central nervous system, α5 is highly expressed in the CA1 area of the hippocampus, the interpeduncular nucleus, the ventral tegmental area (VTA), and the substantia nigra compacta, where nAChRs could potentially influence learning, memory, and drug-seeking behaviors.
Fig 1 (a) Schematic representation of the pentamer arrangement of the subunits in the assembled nAChR. (b) Conserved domains of the nAChR subunit, including amino (N) and carboxy (C) terminals, transmembrane domains (M1–M4) and the intracellular loop.
Application of CHRNA5 Membrane Protein Literature
This article finds that deletion of the alpha 5 nAChR subunit enhances ethanol-induced hypothermia, hypnosis, and anxiolytic-like response compared to wild-type controls. Alpha 5 nAChR is involved in some but not all behavioral effects of ethanol, emphasizing the importance of nAChRs as a possible target for the treatment of alcohol dependence.
This paper shows that CHRNA5 rs16969968 and rs2036527 polymorphisms are associated with higher success rate in the smoking cessation in women.
This article finds that the alpha 5 subunit can occupy the position of a nonbinding subunit or replace β2 subunit involved in the canonical binding site.
This article shows that a heteromeric assembly of α3, β4 and perhaps α5 subunits is involved in the activation step of the catecholamine secretion process and is not blocked by the snake toxin α-bungarotoxin.
This article observes that the α5 subunit is directly involved in multiple phenotypes.
CHRNA5 Preparation Options
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