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Alternative splicing of G protein-coupled receptors: physiology and pathophysiology

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Abstract

The G protein-coupled receptors (GPCRs) are a superfamily of transmembrane receptors that have a broad distribution and can collectively recognise a diverse array of ligands. Activation or inhibition of GPCR signalling can affect many (patho)physiological processes, and consequently they are a major target for existing and emerging drug therapies. A common observation has been that the pharmacological, signalling and regulatory properties of GPCRs can differ in a cell- and tissue-specific manner. Such “phenotypic” diversity might be attributable to post-translational modifications and/or association of GPCRs with accessory proteins, however, post-transcriptional mechanisms are also likely to contribute. Although approximately 50% of GPCR genes are intronless, those that possess introns can undergo alternative splicing, generating GPCR subtype isoforms that may differ in their pharmacological, signalling and regulatory properties. In this review we shall highlight recent research into GPCR splice variation and discuss the potential consequences this might have for GPCR function in health and disease.

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Acknowledgements

We would like to thank Drs. Carl Nelson and Gary Willars (University of Leicester) for helpful comments and suggestions on earlier drafts of this review.

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  1. Department of Cell Physiology and Pharmacology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester, LE1 9HN, UK

    Danijela Markovic & R. A. John Challiss

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Correspondence to R. A. John Challiss.

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Markovic, D., Challiss, R.A.J. Alternative splicing of G protein-coupled receptors: physiology and pathophysiology. Cell. Mol. Life Sci. 66, 3337–3352 (2009). https://doi.org/10.1007/s00018-009-0093-4

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