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Disruption of lipid rafts enhances coupling of G‐proteins to non‐raft associated delta opioid receptors in HEK293 cells
Author(s) -
Levitt Erica Sawyer,
Traynor John R
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a430-b
Subject(s) - lipid raft , raft , g protein coupled receptor , receptor , caveolae , chemistry , δ opioid receptor , microbiology and biotechnology , agonist , lipid microdomain , g protein , signal transduction , biochemistry , biology , membrane , organic chemistry , copolymer , polymer
G‐protein coupled receptor (GPCR) distribution at the cell surface is not homogeneous, but rather GPCRs can localize to different compartments of the plasma membrane. Recently, mu and kappa opioid receptors have been shown to compartmentalize to membrane microdomains known as lipid rafts, which are highly enriched in cholesterol and sphingolipids. Disruption of these lipid rafts with the cholesterol depleting agent methyl‐β‐cyclodextrin (MβCD) leads to alterations in acute and chronic cellular signaling. In these studies, membrane localization of delta opioid receptors in HEK293 cells was determined using detergent‐resistant sucrose gradient ultracentrifugation. In contrast to the mu and kappa opioid receptors, we have found that delta opioid receptors are located in transferrin containing non‐raft fractions, rather than caveolin containing raft fractions. This localization of delta opioid receptors to the non‐raft fraction does not change upon treatment with the delta agonist DPDPE (1μM, 5 min). However, disruption of lipid rafts by MβCD enhances the ability of delta agonists to stimulate GTPγ 35 S binding. These findings indicate that upon disruption of lipid rafts, raft associated G‐proteins are able to couple to the non‐raft associated delta receptor to enhance G‐protein signaling. Supported by NIH grants DA04087 and GM07767.