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Papers In Press, published online ahead of print September 5, 2000
J. Biol. Chem, 10.1074/jbc.C000576200
Submitted on August 24, 2000
Revised on September 1, 2000
Accepted on September 5, 2000

Role of Sterols in Modulating the Human mu -Opioid Receptor Function in Saccharomyces cerevisiae

Bernard Lagane, Gerald Gaibelet, Eliane Meilhoc, Jean-Michel Masson, Laurence Cezanne, and Andre Lopez

Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, Toulouse 31077

Corresponding Author: lopez{at}ipbs.fr

Abstract: This study provides evidence that the differences in membrane composition found from one cell type to another can represent a limiting factor to recovering the functionality of transmembrane proteins when expressed in heterologous systems. Restoring the properties of the human µ-opioid receptor in yeast (S. cerevisiae) similar to those observed in native cells, was achieved by replacing ergosterol from yeast by cholesterol, which is normally found in mammalian plasma membranes. The results suggest that these two sterols have opposite effects with respect to the ligand binding function of the receptor. Ergosterol was found to constrain the µ-opioid receptor in an inactive state in yeast plasma membranes and cannot replace cholesterol in activating it. These data differ from previous works dealing with the function of related G-protein coupled receptors (GPCR) in ergosterol-enriched membranes. This suggests that structural requirements of GPCR with respect to their modulation by lipid components differ from one protein to another. As a consequence, we assume that the presence of appropriate lipids around transmembrane proteins determines their function. This highlights the functional significance of lateral heterogeneities of membrane components within biological membranes.


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