Selectivity and functional consequences of interactions of family A G protein-coupled receptors with neurochondrin and periplakin

Ward, R. J., Jenkins, L. and Milligan, G. (2009) Selectivity and functional consequences of interactions of family A G protein-coupled receptors with neurochondrin and periplakin. Journal of Neurochemistry, 109(1), pp. 182-192. (doi: 10.1111/j.1471-4159.2009.05918.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1471-4159.2009.05918.x

Abstract

A wide range of intracellular proteins have been demonstrated to interact with individual G protein-coupled receptors (GPCRs) and, in certain cases, to modulate their function or trafficking. However, in only a few cases have the GPCR selectivity of such interactions been investigated. Interactions between the intracellular C-terminal tails of 44 GPCRs and both neurochondrin and periplakin were assessed in pull-down studies. 23 of these interacted with neurochondrin and periplakin, 10 interacted with neither whilst nine interacted with only neurochondrin and two with only periplakin. When appropriate GIP-interacting Gq/G11-coupled GPCRs were expressed in cells inducibly expressing neurochondrin or periplakin this resulted in a reduction in the increase in intracellular [Ca2+] in response to agonist. However, induction of neurochondrin or periplakin was without functional consequences for GPCRs with which they did not interact. Unlike intracellular [Ca2+] signals, induction of expression of either interacting protein did not inhibit agonist-mediated ERK1/2 MAPK phosphorylation. These data indicate that both periplakin and neurochondrin can interact with a wide range of GPCRs and modulate function selectively. Details of the structure of the intracellular C-terminal tail of individual receptors will be required to fully understand the basis of such selectivity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ward, Dr Richard and Jenkins, Mrs Laura and Milligan, Professor Graeme
Authors: Ward, R. J., Jenkins, L., and Milligan, G.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Journal of Neurochemistry
Publisher:Wiley-Blackwell Publishing Ltd.
ISSN:0022-3042
ISSN (Online):1471-4159
Published Online:23 January 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
389781The quaternary structure of G-protein coupled receptors - implications for function drug design. Programme grant support renewalGraeme MilliganMedical Research Council (MRC)G9811527Institute of Neuroscience and Psychology
374281Protein interactions and compartmentalisation in cell signallingWalter KolchMedical Research Council (MRC)G0400053Biochemistry & Cell Biology