Cholesterol depletion induces dynamic confinement of the G-protein coupled serotonin(1A) receptor in the plasma membrane of living cells
- PMID: 17292852
- DOI: 10.1016/j.bbamem.2007.01.002
Cholesterol depletion induces dynamic confinement of the G-protein coupled serotonin(1A) receptor in the plasma membrane of living cells
Abstract
Cholesterol is an essential constituent of eukaryotic membranes and plays a crucial role in membrane organization, dynamics, function, and sorting. It is often found distributed non-randomly in domains or pools in biological and model membranes and is thought to contribute to a segregated distribution of membrane constituents. Signal transduction events mediated by seven transmembrane domain G-protein coupled receptors (GPCRs) are the primary means by which cells communicate with and respond to their external environment. We analyzed the role of cholesterol in the plasma membrane organization of the G-protein coupled serotonin(1A) receptor by fluorescence recovery after photobleaching (FRAP) measurements with varying bleach spot sizes. Our results show that lateral diffusion parameters of serotonin(1A) receptors in normal cells are consistent with models describing diffusion of molecules in a homogenous membrane. Interestingly, these characteristics are altered in cholesterol-depleted cells in a manner that is consistent with dynamic confinement of serotonin(1A) receptors in the plasma membrane. Importantly, analysis of ligand binding and downstream signaling of the serotonin(1A) receptor suggests that receptor function is affected in a significantly different manner when intact cells or isolated membranes are depleted of cholesterol. These results assume significance in the context of interpreting effects of cholesterol depletion on diffusion characteristics of membrane proteins in particular, and cholesterol-dependent cellular processes in general.
Similar articles
-
Membrane organization and dynamics of the serotonin1A receptor in live cells.J Neurochem. 2011 Mar;116(5):726-33. doi: 10.1111/j.1471-4159.2010.07037.x. Epub 2011 Jan 7. J Neurochem. 2011. PMID: 21214564 Review.
-
Membrane cholesterol depletion from live cells enhances the function of human serotonin(1A) receptors.Biochem Biophys Res Commun. 2009 Nov 13;389(2):333-7. doi: 10.1016/j.bbrc.2009.08.148. Epub 2009 Aug 31. Biochem Biophys Res Commun. 2009. PMID: 19723504
-
Role of cholesterol in the function and organization of G-protein coupled receptors.Prog Lipid Res. 2006 Jul;45(4):295-333. doi: 10.1016/j.plipres.2006.02.002. Epub 2006 Mar 20. Prog Lipid Res. 2006. PMID: 16616960 Review.
-
Cholesterol depletion modulates detergent resistant fraction of human serotonin(1A) receptors.Mol Membr Biol. 2012 Nov;29(7):290-8. doi: 10.3109/09687688.2012.688147. Epub 2012 May 18. Mol Membr Biol. 2012. PMID: 22594670
-
Chronic cholesterol depletion using statin impairs the function and dynamics of human serotonin(1A) receptors.Biochemistry. 2010 Jul 6;49(26):5426-35. doi: 10.1021/bi100276b. Biochemistry. 2010. PMID: 20521763
Cited by
-
Cholesterol modulates the dimer interface of the β₂-adrenergic receptor via cholesterol occupancy sites.Biophys J. 2014 Mar 18;106(6):1290-300. doi: 10.1016/j.bpj.2014.02.002. Biophys J. 2014. PMID: 24655504 Free PMC article.
-
GFP fluorescence: A few lesser-known nuggets that make it work.J Biosci. 2018 Jul;43(3):421-430. J Biosci. 2018. PMID: 30002261
-
Leishmania donovani infection enhances lateral mobility of macrophage membrane protein which is reversed by liposomal cholesterol.PLoS Negl Trop Dis. 2014 Dec 4;8(12):e3367. doi: 10.1371/journal.pntd.0003367. eCollection 2014 Dec. PLoS Negl Trop Dis. 2014. PMID: 25474261 Free PMC article.
-
The Utility of Fluorescence Recovery after Photobleaching (FRAP) to Study the Plasma Membrane.Membranes (Basel). 2023 May 2;13(5):492. doi: 10.3390/membranes13050492. Membranes (Basel). 2023. PMID: 37233553 Free PMC article. Review.
-
Differential Membrane Dipolar Orientation Induced by Acute and Chronic Cholesterol Depletion.Sci Rep. 2017 Jun 30;7(1):4484. doi: 10.1038/s41598-017-04769-4. Sci Rep. 2017. PMID: 28667339 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous