B. Lagane et al., Role of sterols in modulating the human mu-opioid receptor function in Saccharomyces cerevisiae, J BIOL CHEM, 275(43), 2000, pp. 33197-33200
This study provides evidence that the differences in membrane composition f
ound from one cell type to another can represent a limiting factor to recov
ering the functionality of transmembrane proteins when expressed in heterol
ogous systems. Restoring the properties of the human mu -opioid receptor in
yeast (Saccharomyces cerevisiae), similar to those observed in native cell
s, was achieved by replacing ergosterol from yeast by cholesterol, which is
normally found in mammalian plasma membranes. The results suggest that the
se two sterols have opposite effects with respect to the ligand binding fun
ction of the receptor. Ergosterol was found to constrain the Cr-opioid rece
ptor in an inactive state in yeast plasma membranes and cannot replace chol
esterol in activating it. These data differ from previous works dealing wit
h 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 lipi
ds around transmembrane proteins determines their function. This highlights
the functional significance of lateral heterogeneities of membrane compone
nts within biological membranes.