Selectivity and functional consequences of interactions of family A G protein-coupled receptors with neurochondrin and periplakin.
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 G(q)/G(11)-coupled GPCRs were expressed in cells inducibly expressing neurochondrin or periplakin this resulted in a reduction in the increase in intracellular [Ca(2+)] in response to agonist. However, induction of neurochondrin or periplakin was without functional consequences for GPCRs with which they did not interact. Unlike intracellular [Ca(2+)] 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.
Ward
Richard J
RJ
Molecular Pharmacology Group, Neuroscience and Molecular Pharmacology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
Jenkins
Laura
L
Milligan
Graeme
G
D000818:Animals; D002460:Cell Line; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D051179:Plakins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000145:classification* / Q000378:metabolism / Q000502:physiology*
D009419:Nerve Tissue Proteins; D051179:Plakins; D043562:Receptors, G-Protein-Coupled; C119189:neurochondrin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11