Compartmentation of G-protein-coupled receptors and their signalling components in lipid rafts and caveolae

2005 ◽  
Vol 33 (5) ◽  
pp. 1131 ◽  
Author(s):  
B.P. Head ◽  
P.A. Insel ◽  
H.H. Patel ◽  
D.M. Roth ◽  
R.A. Bundey ◽  
...  
Keyword(s):  
G Protein ◽  
Lipid Rafts ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

Compartmentation of G-protein-coupled receptors and their signalling components in lipid rafts and caveolae

2005 ◽  
Vol 33 (5) ◽  
pp. 1131-1134 ◽  
Author(s):  
P.A. Insel ◽  
B.P. Head ◽  
H.H. Patel ◽  
D.M. Roth ◽  
R.A. Bundey ◽  
...  
Keyword(s):  
G Protein ◽  
Lipid Rafts ◽  
Plasma Membranes ◽  
Subcellular Fractionation ◽  
G Protein Coupled Receptors ◽  
Membrane Microdomains ◽  
Adult Cardiac Myocytes ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) and post-GPCR signalling components are expressed at low overall abundance in plasma membranes, yet they evoke rapid, high-fidelity responses. Considerable evidence suggests that GPCR signalling components are organized together in membrane microdomains, in particular lipid rafts, enriched in cholesterol and sphingolipids, and caveolae, a subset of lipid rafts that also possess the protein caveolin, whose scaffolding domain may serve as an anchor for signalling components. Caveolae were originally identified based on their morphological appearance but their role in compartmentation of GPCR signalling has been primarily studied by biochemical techniques, such as subcellular fractionation and immunoprecipitation. Our recent studies obtained using both microscopic and biochemical methods with adult cardiac myocytes show expression of caveolin not only in surface sarcolemmal domains but also at, or close to, internal regions located at transverse tubules/sarcoplasmic reticulum. Other results show co-localization in lipid rafts/caveolae of AC (adenylyl cyclase), in particular AC6, certain GPCRs, G-proteins and eNOS (endothelial nitric oxide synthase; NOS3), which generates NO, a modulator of AC6. Existence of multiple caveolin-rich microdomains and their expression of multiple modulators of signalling strengthen the evidence that caveolins and lipid rafts/caveolae organize and regulate GPCR signal transduction in eukaryotic cells.

scholarly journals G-protein coupled receptors in lipid rafts and caveolae: how, when and why do they go there?

2004 ◽  
Vol 32 (2) ◽  
pp. 325-338 ◽  
Author(s):  
B Chini ◽  
M Parenti
Keyword(s):  
G Protein ◽  
Lipid Rafts ◽  
G Protein Coupled Receptors ◽  
Fine Tuning ◽  
Membrane Microdomains ◽  
Signalling Molecules ◽  
Cell Functions ◽  
Experimental Approaches ◽  
G Protein Coupled

This review describes the advances in our understanding of the role of G-protein coupled receptor (GPCR) localisation in membrane microdomains known as lipid rafts and caveolae. The growing interest in these specialised regions is due to the recognition that they are involved in the regulation of a number of cell functions, including the fine-tuning of various signalling molecules. As a number of GPCRs have been found to be enriched in lipid rafts and/or caveolae by means of different experimental approaches, we first discuss the pitfalls and uncertainties related to the use of these different procedures. We then analyse the addressing signals that drive and/or stabilise GPCRs in lipid rafts and caveolae, and explore the role of rafts/caveolae in regulating GPCR trafficking, particularly in receptor exo- and endocytosis. Finally, we review the growing evidence that lipid rafts and caveolae participate in the regulation of GPCR signalling by affecting both signalling selectivity and coupling efficacy.

Consequences of lipid raft association on G-protein-coupled receptor function.

2005 ◽  
Vol 72 ◽  
pp. 151-164 ◽  
Author(s):  
Anja Becher ◽  
R. A. Jeffrey McIlhinney
Keyword(s):  
G Protein ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Neurological Disorders ◽  
G Protein Coupled Receptors ◽  
Membrane Microdomains ◽  
Pharmaceutical Drug ◽  
Cellular Processes ◽  
G Protein Coupled ◽  
Specific Membrane

GPCRs (G-protein-coupled receptors) play key roles in many cellular processes, and malfunction may lead to a range of pathologies, including psychiatric and neurological disorders. It is therefore not surprising that this group of receptors supplies a majority of the targets for pharmaceutical drug development. Despite their importance, the mechanisms that regulate their function and signalling still remain only partially understood. Recently, it has become evident that a subset of GPCRs is not homogeneously distributed in the plasma membrane, but localizes instead to specific membrane microdomains known as lipid rafts. Lipid rafts are characterized by their enrichment in cholesterol and sphingolipids, and have been suggested to serve as platforms for a range of cellular signalling complexes. In the present review, we will be discussing the effects of the lipid raft environment on trafficking, signalling and internalization of raft-associated GPCRs.

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