Heteromeric α7β2 Nicotinic Acetylcholine Receptors in the Brain

TY - JOUR

T1 - Heteromeric α7β2 Nicotinic Acetylcholine Receptors in the Brain

AU - Wu, Jie

AU - Liu, Qiang

AU - Tang, Pei

AU - Mikkelsen, Jens D

AU - Shen, Jianxin

AU - Whiteaker, Paul

AU - Yakel, Jerrel L

N1 - Copyright © 2016. Published by Elsevier Ltd.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - The α7 nicotinic acetylcholine receptor (α7 nAChR) is highly expressed in the brain, where it maintains various neuronal functions including (but not limited to) learning and memory. In addition, the protein expression levels of α7 nAChRs are altered in various brain disorders. The classic rule governing α7 nAChR assembly in the mammalian brain was that it was assembled from five α7 subunits to form a homomeric receptor pentamer. However, emerging evidence demonstrates the presence of heteromeric α7 nAChRs in heterologously expressed systems and naturally in brain neurons, where α7 subunits are co-assembled with β2 subunits to form a novel type of α7β2 nAChR. Interestingly, the α7β2 nAChR exhibits distinctive function and pharmacology from traditional homomeric α7 nAChRs. We review recent advances in probing the distribution, function, pharmacology, pathophysiology, and stoichiometry of the heteromeric α7β2 nAChR, which have provided new insights into the understanding of a novel target of cholinergic signaling.

AB - The α7 nicotinic acetylcholine receptor (α7 nAChR) is highly expressed in the brain, where it maintains various neuronal functions including (but not limited to) learning and memory. In addition, the protein expression levels of α7 nAChRs are altered in various brain disorders. The classic rule governing α7 nAChR assembly in the mammalian brain was that it was assembled from five α7 subunits to form a homomeric receptor pentamer. However, emerging evidence demonstrates the presence of heteromeric α7 nAChRs in heterologously expressed systems and naturally in brain neurons, where α7 subunits are co-assembled with β2 subunits to form a novel type of α7β2 nAChR. Interestingly, the α7β2 nAChR exhibits distinctive function and pharmacology from traditional homomeric α7 nAChRs. We review recent advances in probing the distribution, function, pharmacology, pathophysiology, and stoichiometry of the heteromeric α7β2 nAChR, which have provided new insights into the understanding of a novel target of cholinergic signaling.

KW - Journal Article

KW - Review

U2 - 10.1016/j.tips.2016.03.005

DO - 10.1016/j.tips.2016.03.005

M3 - Review

C2 - 27179601

SN - 0165-6147

VL - 37

SP - 562

EP - 574

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

IS - 7

ER -