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Using Sterol Substitution to Probe the Role of Membrane Domains in Membrane Functions

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Lipids

Abstract

Ordered membrane lipid domains rich in sphingolipids and sterols (“lipid rafts”) are thought to be important in many biological processes.  However, it is often difficult to distinguish domain-dependent biological functions from ones that have a specific dependence on sterol, e.g. are dependent upon a protein with a function that is dependent upon its binding to sterol.  Removing cholesterol and replacing it with various sterols with varying abilities to form membrane domains or otherwise alter membrane properties has the potential to help distinguish these cases.  This review describes this strategy, and how it has been applied by various investigators to understand cellular functions.

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Abbreviations

5-HT1A:

5-Hydroxytryptamine (serotonin) receptor 1A

7KC:

7-Ketocholesterol

8-OH-DPAT:

8-Hydroxy-2(di-N-propylamino)tetralin

APP:

Amyloid precursor protein

BSA:

Bovine serum albumin

CCKR:

Cholecystokinin receptor

CD39:

Ecto-nucleoside triphosphate diphosphohydrolase-1

CHO:

Chinese hamster ovary

ΔchoD:

Knock-out of cholesterol oxidase gene

CR3:

Complement receptor 3

DPH:

Diphenylhexatriene

DRM:

Detergent resistant membranes

EGFR:

Epidermal growth factor receptor

ent-cholesterol:

Cholesterol-enantiomer

ER:

Endoplasmic reticulum

ETA:

Endothelin receptor type A

FRET:

Fluorescence resonance energy transfer

GABA:

Gamma-aminobutyric acid

GalR2:

Galanin receptor 2

GM1:

Monosialotetrahexosylganglioside

HIV-1:

Human immunodeficiency virus type 1

HPβCD:

Hydroxypropyl-β-cyclodextrin

IK1:

Intermediate-conductance Ca2+-activated K channels

Ld:

Liquid disordered

Lo:

Liquid ordered

maxi-K:

Large-conductance Ca2+-activated K channels

MβCD:

Methyl-β-cyclodextrin

Mtb:

Mycobacterium tuberculosis

NO:

Nitric oxide

OTR:

Oxytocin receptor

PC:

Phosphatidylcholine

PFO:

Perfringolysin O

ROS:

Reactive oxygen species

SCAP:

SREBP cleavage-activating protein

SFV:

Semliki Forest virus

SMase:

Sphingomyelinase

SREBP:

Sterol regulatory element binding protein

TCR:

T cell receptor

TMADPH:

Trimethylammonium diphenylhexatriene

TLR2:

Toll-like receptor 2

TRPV1:

Transient receptor potential vanilloid 1

VRAC:

Volume-regulated anion current

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Acknowledgments

This work was supported by NIH Grant GM 099892.

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Authors and Affiliations

  1. Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, 11794-5215, USA

    JiHyun Kim & Erwin London

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  1. JiHyun Kim
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  2. Erwin London
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Correspondence to Erwin London.

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Part of the topical collection G. J. Schroepfer, Jr. Memorial Sterol Symposium.

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Kim, J., London, E. Using Sterol Substitution to Probe the Role of Membrane Domains in Membrane Functions. Lipids 50, 721–734 (2015). https://doi.org/10.1007/s11745-015-4007-y

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