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The function of G-protein coupled receptors and membrane cholesterol: specific or general interaction?

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Abstract

Cholesterol is an essential component of eukaryotic membranes and plays a crucial role in membrane organization, dynamics and function. The G-protein coupled receptors (GPCRs) are the largest class of molecules involved in signal transduction across membranes and constitute ~1–2% of the human genome. GPCRs have emerged as major targets for the development of novel drug candidates in all clinical areas due to their involvement in the generation of multitude of cellular responses. Membrane cholesterol has been reported to have a modulatory role in the function of a number of GPCRs. This effect could either be due to specific molecular interaction between cholesterol and GPCR, or due to alterations in the membrane physical properties induced by cholesterol. Alternatively, membrane cholesterol could modulate receptor function by occupying the ‘nonannular’ sites around the receptor. In this review, we have highlighted the nature of cholesterol dependence of GPCR function taking a few known examples.

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Abbreviations

5-HT:

5-Hydroxytryptamine

7-DHC:

7-Dehydrocholesterol

8-OH-DPAT:

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

CCK:

Cholecystokinin

DPH:

1,6-Diphenyl-1,3,5-hexatriene

GPCR:

G-protein coupled receptor

FRET:

Fluorescence resonance energy transfer

MβCD:

Methyl-β-cyclodextrin

SLOS:

Smith–Lemli–Opitz syndrome

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Acknowledgements

Work in A.C.’s laboratory was supported by the Council of Scientific and Industrial Research, Department of Biotechnology, Life Sciences Research Board, and the International Society for Neurochemistry. Y.D.P. thanks the Council of Scientific and Industrial Research for the award of a Senior Research Fellowship. A.C. is an Adjunct Professor at the Special Centre for Molecular Medicine of Jawaharlal Nehru University (New Delhi, India), and Honorary Professor of the Jawaharlal Nehru Centre for Advanced Scientific Research, (Bangalore, India). We gratefully acknowledge Roopali Saxena for her help in generating Fig. 1. We thank Drs. Thomas J. Pucadyil and Shanti Kalipatnapu for helpful discussions, and members of our laboratory for critically reading the manuscript.

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  1. Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad, 500 007, India

    Yamuna Devi Paila & Amitabha Chattopadhyay

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  2. Amitabha Chattopadhyay
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Correspondence to Amitabha Chattopadhyay.

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Paila, Y.D., Chattopadhyay, A. The function of G-protein coupled receptors and membrane cholesterol: specific or general interaction?. Glycoconj J 26, 711–720 (2009). https://doi.org/10.1007/s10719-008-9218-5

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  • DOI: https://doi.org/10.1007/s10719-008-9218-5

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