Alternative splicing of G protein-coupled receptors: physiology and pathophysiology.
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.
Markovic
Danijela
D
Department of Cell Physiology and Pharmacology, University of Leicester, Henry Wellcome Building, Leicester, UK. dm186@leicester.ac.uk
Challiss
R A John
RA
D017398:Alternative Splicing / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009765:Obesity / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011968:Receptors, Histamine / Q000378:metabolism / Q000502:physiology; D012140:Respiratory Tract Diseases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D007155:Immunologic Factors; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine