PMID: 9545586May 16, 1998Paper

Where does cholesterol act during activation of the nicotinic acetylcholine receptor?

Biochimica Et Biophysica Acta
George H AddonaK W Miller

Abstract

Why agonist-induced activation of the nicotinic acetylcholine receptor (nAcChoR) fails completely in the absence of cholesterol is unknown. Affinity-purified nAcChoRs from Torpedo reconstituted into 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine/1, 2-dioleoyl-sn-glycero-3-phosphate/steroid bilayers at mole ratios of 58:12:30 were used to distinguish between three regions of the membrane where cholesterol might act: the lipid bilayer, the lipid-protein interface, or sites within the protein itself. In the bilayer, the role of fluidity has been ruled out and certain neutral lipids can substitute for cholesterol [C. Sunshine, M.G. McNamee, Biochim. Biophys. Acta 1191 (1994) 59-64]; therefore, we first tested the hypothesis that flip-flop of cholesterol across the membrane is important; a plausible mechanism might be the relief of mechanical bending strain induced by a conformation change that expands the two leaflets of the bilayer asymmetrically. Cholesterol analogs prevented from flipping by charged groups attached to the 3-position's hydroxyl supported channel opening, contrary to this hypothesis. The second hypothesis is that interstitial cholesterol binding sites exist deep within the nAcChoR that must be occupied for channel ...Continue Reading

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Citations

Feb 11, 2005·The Journal of Membrane Biology·E J Westover, D F Covey
Jun 1, 2005·Biophysical Chemistry·Sergej KakorinEberhard Neumann
Feb 6, 2003·Biophysical Chemistry·Miroslav Karabaliev, Valery Kochev
Sep 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Grace BranniganMichael L Klein
Oct 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·John F LeiteHenry A Lester
Oct 16, 2007·The Journal of Biological Chemistry·Lavanya RajagopalanWilliam E Brownell
Jun 27, 2006·The AAPS Journal·Michael Cascio
Aug 18, 2010·Neuropharmacology·John E Baenziger, Pierre-Jean Corringer
Jan 25, 2003·Biochimica Et Biophysica Acta·George H AddonaKeith W Miller
Dec 2, 2004·Brain Research. Brain Research Reviews·F J Barrantes
Nov 3, 2004·Biochimica Et Biophysica Acta·Anthony G Lee
Apr 18, 2006·Progress in Lipid Research·Thomas J Pucadyil, Amitabha Chattopadhyay
Mar 23, 2010·Biophysical Journal·Raymond M Sturgeon, John E Baenziger
Mar 21, 2015·Biochimica Et Biophysica Acta·John E BaenzigerJiayin Sun
Apr 4, 2015·Biochimica Et Biophysica Acta·Francisco J Barrantes
May 6, 2003·Biochimica Et Biophysica Acta·A G Lee
Apr 27, 2016·The Journal of Membrane Biology·Carlos A Báez-PagánJosé A Lasalde-Dominicci
Sep 11, 2013·The Journal of Biological Chemistry·Avia Rosenhouse-DantskerIrena Levitan
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May 8, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Jean-Pierre Changeux
Sep 18, 2018·Pakistan Journal of Biological Sciences : PJBS·Wuyi Liu, Kunkai Su
Apr 21, 2020·Biochimica Et Biophysica Acta. Biomembranes·Mackenzie J Thompson, John E Baenziger
Jul 10, 2021·The Journal of Chemical Physics·Liam Sharp, Grace Brannigan

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