Imperial College London
Alternate

Professor Sir Steve Bloom FMedSci, FRS

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Departmental Academic REF2014 Lead
 
 
 
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Contact

 

+44 (0)20 7594 9048s.bloom Website

 
 
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Assistant

 

Ms Keda Price-Cousins +44 (0)20 7594 9048

 
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Location

 

6N3Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Buenaventura:2017:10.2337/db17-0639,
author = {Buenaventura, T and Kanda, N and Douzenis, PC and Jones, B and Bloom, SR and Chabosseau, P and Corrêa, IR and Bosco, D and Piemonti, L and Marchetti, P and Johnson, PR and Shapiro, AJ and Rutter, GA and Tomas, A},
doi = {10.2337/db17-0639},
journal = {Diabetes},
pages = {385--399},
title = {A targeted RNAi screen identifies endocytic trafficking factors that control GLP-1 receptor signaling in pancreatic beta cells},
url = {http://dx.doi.org/10.2337/db17-0639},
volume = {67},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The GLP-1 receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Since endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we have screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic beta cells. We identify five (clathrin, dynamin1, AP2, SNX27 and SNX1) that increase and four (HIP1, HIP14, GASP-1 and Nedd4) that decrease insulin secretion from murine insulinoma MIN6B1 cells in response to the GLP-1 analogue exendin-4. The roles of Huntingtin-interacting protein 1 (HIP1) and the endosomal sorting nexins SNX1 and SNX27 were further characterized in mouse and human beta cell lines and human islets. While HIP1 was required for the coupling of cell surface GLP-1R activation with clathrin-dependent endocytosis, the sorting nexins were found to control the balance between GLP-1R plasma membrane recycling and lysosomal degradation, and, in doing so, determine the overall beta cell incretin responses. We thus identify key modulators of GLP-1R trafficking and signaling that might provide novel targets to enhance insulin secretion in T2D.
AU  - Buenaventura,T
AU  - Kanda,N
AU  - Douzenis,PC
AU  - Jones,B
AU  - Bloom,SR
AU  - Chabosseau,P
AU  - Corrêa,IR
AU  - Bosco,D
AU  - Piemonti,L
AU  - Marchetti,P
AU  - Johnson,PR
AU  - Shapiro,AJ
AU  - Rutter,GA
AU  - Tomas,A
DO  - 10.2337/db17-0639
EP  - 399
PY  - 2017///
SN  - 0012-1797
SP  - 385
TI  - A targeted RNAi screen identifies endocytic trafficking factors that control GLP-1 receptor signaling in pancreatic beta cells
T2  - Diabetes
UR  - http://dx.doi.org/10.2337/db17-0639
UR  - http://hdl.handle.net/10044/1/55694
VL  - 67
ER  -
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