Imperial College London
Alternate

DrDavidHodson

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Senior Lecturer (non-clinical)
 
 
 
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Contact

 

+44 (0)20 7594 1713d.hodson Website

 
 
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Location

 

329ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cegla:2017:10.1210/en.2016-1755,
author = {Cegla, J and Jones, BJ and Gardiner, JV and Hodson, DJ and Marjot, T and McGlone, ER and Tan, TM and Bloom, SR},
doi = {10.1210/en.2016-1755},
journal = {Endocrinology},
pages = {2680--2693},
title = {RAMP2 influences glucagon receptor pharmacology via trafficking and signaling},
url = {http://dx.doi.org/10.1210/en.2016-1755},
volume = {158},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Endogenous satiety hormones provide an attractive target for obesity drugs. Glucagon causes weight loss by reducing food intake and increasing energy expenditure. To further understand the cellular mechanisms by which glucagon and related ligands activate the glucagon receptor (GCGR), we investigated the interaction of the GCGR with receptor activity modifying protein (RAMP)2, a member of the family of receptor activity modifying proteins. We used a combination of competition binding experiments, cell surface enzyme-linked immunosorbent assay, functional assays assessing the Gαs and Gαq pathways and β-arrestin recruitment, and small interfering RNA knockdown to examine the effect of RAMP2 on the GCGR. Ligands tested were glucagon; glucagonlike peptide-1 (GLP-1); oxyntomodulin; and analog G(X), a GLP-1/glucagon coagonist developed in-house. Confocal microscopy was used to assess whether RAMP2 affects the subcellular distribution of GCGR. Here we demonstrate that coexpression of RAMP2 and the GCGR results in reduced cell surface expression of the GCGR. This was confirmed by confocal microscopy, which demonstrated that RAMP2 colocalizes with the GCGR and causes significant GCGR cellular redistribution. Furthermore, the presence of RAMP2 influences signaling through the Gαs and Gαq pathways, as well as recruitment of β-arrestin. This work suggests that RAMP2 may modify the agonist activity and trafficking of the GCGR, with potential relevance to production of new peptide analogs with selective agonist activities.
AU  - Cegla,J
AU  - Jones,BJ
AU  - Gardiner,JV
AU  - Hodson,DJ
AU  - Marjot,T
AU  - McGlone,ER
AU  - Tan,TM
AU  - Bloom,SR
DO  - 10.1210/en.2016-1755
EP  - 2693
PY  - 2017///
SN  - 0013-7227
SP  - 2680
TI  - RAMP2 influences glucagon receptor pharmacology via trafficking and signaling
T2  - Endocrinology
UR  - http://dx.doi.org/10.1210/en.2016-1755
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000406757000024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/53855
VL  - 158
ER  -
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