Cholesterol depletion induces dynamic confinement of the G-protein coupled serotonin1A receptor in the plasma membrane of living cells Export

@article{citeulike:1147042, 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 serotonin1A receptor by fluorescence recovery after photobleaching (FRAP) measurements with varying bleach spot sizes. Our results show that lateral diffusion parameters of serotonin1A 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 serotonin1A receptors in the plasma membrane. Importantly, analysis of ligand binding and downstream signaling of the serotonin1A 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.}, author = {Pucadyil, Thomas J. and Chattopadhyay, Amitabha}, citeulike-article-id = {1147042}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bbamem.2007.01.002}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17292852}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17292852}, citeulike-linkout-3 = {http://www.sciencedirect.com/science/article/B6T1T-4MT5K3C-1/2/ac4eaa117952bd55ef7e6cbe2441b918}, doi = {10.1016/j.bbamem.2007.01.002}, journal = {Biochimica et Biophysica Acta (BBA) - Biomembranes}, keywords = {5-ht1a, cholesterol, g-protein}, month = {March}, number = {3}, pages = {655--668}, posted-at = {2007-03-09 15:50:31}, priority = {2}, title = {Cholesterol depletion induces dynamic confinement of the G-protein coupled serotonin1A receptor in the plasma membrane of living cells}, url = {http://dx.doi.org/10.1016/j.bbamem.2007.01.002}, volume = {1768}, year = {2007} }

TY - JOUR ID - citeulike:1147042 L3 - citeulike-article-id:1147042 N2 - 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 serotonin1A receptor by fluorescence recovery after photobleaching (FRAP) measurements with varying bleach spot sizes. Our results show that lateral diffusion parameters of serotonin1A 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 serotonin1A receptors in the plasma membrane. Importantly, analysis of ligand binding and downstream signaling of the serotonin1A 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. IS - 3 JF - Biochimica et Biophysica Acta (BBA) - Biomembranes EP - 668 TI - Cholesterol depletion induces dynamic confinement of the G-protein coupled serotonin1A receptor in the plasma membrane of living cells VL - 1768 SP - 655 KW - 5-ht1a KW - cholesterol KW - g-protein AU - Pucadyil, Thomas AU - Chattopadhyay, Amitabha PY - 2007/03// UR - http://dx.doi.org/10.1016/j.bbamem.2007.01.002 ER -