NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor.

Cellular and Molecular Life Sciences : CMLS
Simone MazzaferroSteven M Sine

Abstract

Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of pentameric ligand-gated ion channels, and in neuronal tissues, are assembled from various types of α- and β-subunits. Furthermore, the subunits α4 and β2 assemble in two predominant stoichiometric forms, (α4)2(β2)3 and (α4)3(β2)2, forming receptors with dramatically different sensitivity to agonists and allosteric modulators. However, mechanisms by which the two stoichiometric forms are regulated are not known. Here, using heterologous expression in mammalian cells, single-channel patch-clamp electrophysiology, and calcium imaging, we show that the ER-resident protein NACHO selectively promotes the expression of the (α4)2(β2)3 stoichiometry, whereas the cytosolic molecular chaperone 14-3-3η selectively promotes the expression of the (α4)3(β2)2 stoichiometry. Thus, NACHO and 14-3-3η are potential physiological regulators of subunit stoichiometry, and are potential drug targets for re-balancing the stoichiometry in pathological conditions involving α4β2 nAChRs such as nicotine dependence and epilepsy.

References

Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·W S PearD Baltimore
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S M Sine
Jan 16, 2003·Molecular Pharmacology·Mark E NelsonJon Lindstrom
Aug 16, 2003·Epilepsia·John O WilloughbyVaughn Eaton
Jan 7, 2004·Nature Reviews. Neuroscience·Steven R Laviolette, Derek van der Kooy
May 29, 2004·Trends in Pharmacological Sciences·Federico Dajas-Bailador, Susan Wonnacott
Aug 26, 2006·Epilepsy & Behavior : E&B·Eylert Brodtkorb, Fabienne Picard
Aug 30, 2008·Neuropharmacology·Neil S Millar, Cecilia Gotti
Jan 8, 2009·Physiological Reviews·Edson X AlbuquerqueScott W Rogers
May 2, 2009·Biochemical Pharmacology·Martin SarterWilliam M Howe
Sep 2, 2009·Nature Reviews. Drug Discovery·Antoine TalyJean-Pierre Changeux
Dec 29, 2010·The Journal of General Physiology·Rahul SrinivasanHenry A Lester
Jul 29, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tresa M McGranahanT K Booker
Aug 29, 2012·Pharmacology & Therapeutics·Raymond HurstDaniel Bertrand
Nov 13, 2012·Cold Spring Harbor Perspectives in Medicine·Marina R Picciotto, Paul J Kenny
Sep 7, 2014·The Journal of Biological Chemistry·Weston A NicholsJulie M Miwa
Dec 3, 2014·Neuropharmacology·Michele ZoliCecilia Gotti
May 6, 2015·Neurology·Pantelis P Pavlakis, Laurie M Douglass
Aug 14, 2015·The Journal of Biological Chemistry·Ashley M FoxChristopher I Richards
Feb 16, 2016·Neuron·Shenyan GuDavid S Bredt
Apr 5, 2016·Structure·Claudio L Morales-PerezRyan E Hibbs
Jun 30, 2016·The Journal of General Physiology·Nuriya MukhtasimovaSteven M Sine
Apr 27, 2017·Cell Reports·Jose A MattaDavid S Bredt
Apr 30, 2017·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yongan SunMin Wang
Jul 13, 2017·Molecular Pharmacology·Kristen E DeDominicisRobert P Yasuda

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Methods Mentioned

BETA
fluorescence imaging
transfection
two-hybrid

Software Mentioned

Excel
Prism
GraphPad
TACFit
TAC
pClamp
Acquire
NACHO
GenScript
Metamorph

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