Receptor activity-modifying protein-dependent impairment of calcitonin receptor splice variant Δ(1-47)hCT((a)) function

Show simple item record Qi, T en Dong, M en Watkins, Harriet en Wootten, D en Miller, LJ en Hay, Deborah en 2013-09-26T04:57:29Z en 2013-02 en
dc.identifier.citation British Journal of Pharmacology 168(3):644-657 05 Sep 2012 en
dc.identifier.issn 0007-1188 en
dc.identifier.uri en
dc.description.abstract Background and Purpose Alternative splicing expands proteome diversity to GPCRs. Distinct receptor variants have been identified for a secretin family GPCR, the calcitonin receptor (CTR). The possible functional contributions of these receptor variants are further altered by their potential interactions with receptor activity-modifying proteins (RAMPs). One variant of the human CTR lacks the first 47 residues at its N terminus [Δ(1–47)hCT(a)]. However, very little is known about the pharmacology of this variant or its ability to interact with RAMPs to form amylin receptors. Experimental Approach Δ(1–47)hCT(a) was characterized both with and without RAMPs in Cos7 and/or HEK293S cells. The receptor expression (ELISA assays) and function (cAMP and pERK1/2 assays) for up to six agonists and two antagonists were determined. Key Results Despite lacking 47 residues at the N terminus, Δ(1–47)hCT(a) was still able to express at the cell surface, but displayed a generalized reduction in peptide potency. Δ(1–47)hCT(a) retained its ability to interact with RAMP1 and formed a functional amylin receptor; this also appeared to be the case with RAMP3. On the other hand, its interaction with RAMP2 and resultant amylin receptor was reduced to a greater extent. Conclusions and Implications Δ(1–47)hCT(a) acts as a functional receptor at the cell surface. It exhibits altered receptor function, depending on whether it associates with a RAMP and which RAMP it interacts with. Therefore, the presence of this variant in tissues will potentially contribute to altered peptide binding and signalling, depending on the RAMP distribution in tissues. en
dc.relation.ispartofseries British Journal of Pharmacology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.title Receptor activity-modifying protein-dependent impairment of calcitonin receptor splice variant Δ(1-47)hCT((a)) function en
dc.type Journal Article en
dc.identifier.doi 10.1111/j.1476-5381.2012.02197.x en
pubs.issue 3 en
pubs.begin-page 644 en
pubs.volume 168 en
dc.identifier.pmid 22946511 en en
pubs.end-page 657 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 360932 en Science en Biological Sciences en Science Research en Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1476-5381 en
pubs.record-created-at-source-date 2012-11-29 en
pubs.dimensions-id 22946511 en

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