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Caveolin, Sterol Carrier Protein-2, Membrane Cholesterol-Rich Microdomains and Intracellular Cholesterol Trafficking

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Cholesterol Binding and Cholesterol Transport Proteins:

Part of the book series: Subcellular Biochemistry ((SCBI,volume 51))

Abstract

While the existence of membrane lateral microdomains has been known for over 30 years, interest in these structures accelerated in the past decade due to the discovery that cholesterol-rich microdomains serve important biological functions. It is increasingly appreciated that cholesterol-rich microdomains in the plasma membranes of eukaryotic cells represent an organizing nexus for multiple cellular proteins involved in transmembrane nutrient uptake (cholesterol, fatty acid, glucose, etc.), cell-signaling, immune recognition, pathogen entry, and many other roles. Despite these advances, however, relatively little is known regarding the organization of cholesterol itself in these plasma membrane microdomains. Although a variety of non-sterol markers indicate the presence of microdomains in the plasma membranes of living cells, none of these studies have demonstrated that cholesterol is enriched in these microdomains in living cells. Further, the role of cholesterol-rich membrane microdomains as targets for intracellular cholesterol trafficking proteins such as sterol carrier protein-2 (SCP-2) that facilitate cholesterol uptake and transcellular transport for targeting storage (cholesterol esters) or efflux is only beginning to be understood. Herein, we summarize the background as well as recent progress in this field that has advanced our understanding of these issues.

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Abbreviations

ABCA1, ABCG1, ABCG5,:

refer to ATP-binding cassette proteins

and ABCG8:

A1, G1, G5, and G8 respectively

BC-θ:

biotinylated Cθ–toxin

CT-B:

cholera toxin subunit B

DChol:

6-dansyl-cholestanol

DHE:

dehydroergosterol

DiD:

1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt(DiIC18(5))

DRM:

detergent resistant membranes

FRET:

fluorescence resonance energy transfer

HDL:

high density lipoprotein

L-FABP:

liver fatty acid binding protein

LSCM:

laser scanning confocal microscopy

MPLSM:

multiphoton laser scanning microscopy

MβCD:

Methyl-β-cyclodextrin

NBD-cholesterol:

22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β -ol

Pgp:

P-glycoprotein

PM:

plasma membrane

N-Rh-DOPE:

1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine-N-(Lissamine Rhodamine B Sulfonyl) (Ammonium Salt)

SCP-2:

sterol carrier protein-2

SRB1:

scavenger receptor B1

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Acknowledgements

This work was supported in part by the USPHS National Institutes of Health GM31651 (FS, ABK) and DK70965 (BPA). The helpful technical assistance of Ms. Kerstin Landrock was much appreciated.

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Schroeder, F., Huang, H., McIntosh, A.L., Atshaves, B.P., Martin, G.G., Kier, A.B. (2010). Caveolin, Sterol Carrier Protein-2, Membrane Cholesterol-Rich Microdomains and Intracellular Cholesterol Trafficking. In: Harris, J. (eds) Cholesterol Binding and Cholesterol Transport Proteins:. Subcellular Biochemistry, vol 51. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8622-8_10

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