CCR5 internalisation and signalling have different dependence on membrane lipid raft integrity

Moyano Cardaba, Clara, Kerr, Jason S. and Mueller, Anja ORCID: (2008) CCR5 internalisation and signalling have different dependence on membrane lipid raft integrity. Cellular Signalling, 20 (9). pp. 1687-1694.

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The chemokine receptor, CCR5, acts as a co-receptor for human immunodeficiency virus entry into cells. CCR5 has been shown to be targeted to cholesterol- and sphingolipid-rich membrane microdomains termed lipid rafts or caveolae. Cholesterol is essential for CCL4 binding to CCR5 and for keeping the conformational integrity of the receptor. Filipin treatment leads to loss of caveolin-1 from the membrane and therefore to a collapse of the caveolae. We have found here that sequestration of membrane cholesterol with filipin did not affect receptor signalling, however a loss of ligand-induced internalisation of CCR5 was observed. Cholesterol extraction with methyl-ß-cyclodextrin (MCD) reduced signalling through CCR5 as measured by release of intracellular Ca2+ and completely abolished the inhibition of forskolin-stimulated cAMP accumulation with no effect on internalisation. Pertussis toxin (PTX) treatment inhibited the intracellular release of calcium that is transduced via Gai G-proteins. Depletion of cholesterol destroyed microdomains in the membrane and switched CCR5/G-protein coupling to a PTX-independent G-protein. We conclude that cholesterol in the membrane is essential for CCR5 signalling via the Gai G-protein subunit, and that integrity of lipid rafts is not essential for effective CCR5 internalisation however it is crucial for proper CCR5 signal transduction via Gai G-proteins.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Science > Research Groups > Pharmaceutical Cell Biology (former - to 2017)
Faculty of Science > Research Groups > Molecular and Tissue Pharmacology
Depositing User: Rachel Smith
Date Deposited: 17 Mar 2011 10:15
Last Modified: 24 Oct 2022 00:41
DOI: 10.1016/j.cellsig.2008.05.014

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