Imperial College London
Portrait Picture

ProfessorAylinHanyaloglu

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor in Molecular Medicine
 
 
 
//

Contact

 

+44 (0)20 7594 2128a.hanyaloglu Website

 
 
//

Assistant

 

Miss Kiran Dosanjh +44 (0)20 7594 2176

 
//

Location

 

2009Institute of Reproductive and Developmental BiologyHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Buenaventura:2019:10.1371/journal.pbio.3000097,
author = {Buenaventura, T and Bitsi, S and Laughlin, WE and Burgoyne, T and Lyu, Z and Oqua, AI and Norman, H and McGlone, ER and Klymchenko, AS and Corrêa, IR and Walker, A and Inoue, A and Hanyaloglu, A and Grimes, J and Koszegi, Z and Calebiro, D and Rutter, GA and Bloom, SR and Jones, B and Tomas, A},
doi = {10.1371/journal.pbio.3000097},
journal = {PLoS Biology},
pages = {1--40},
title = {Agonist-induced membrane nanodomain clustering drives GLP-1 receptor responses in pancreatic beta cells.},
url = {http://dx.doi.org/10.1371/journal.pbio.3000097},
volume = {17},
year = {2019}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The glucagon-like peptide-1 receptor (GLP-1R), a key pharmacological target in type 2 diabetes (T2D) and obesity, undergoes rapid endocytosis after stimulation by endogenous and therapeutic agonists. We have previously highlighted the relevance of this process in fine-tuning GLP-1R responses in pancreatic beta cells to control insulin secretion. In the present study, we demonstrate an important role for the translocation of active GLP-1Rs into liquid-ordered plasma membrane nanodomains, which act as hotspots for optimal coordination of intracellular signaling and clathrin-mediated endocytosis. This process is dynamically regulated by agonist binding through palmitoylation of the GLP-1R at its carboxyl-terminal tail. Biased GLP-1R agonists and small molecule allosteric modulation both influence GLP-1R palmitoylation, clustering, nanodomain signaling, and internalization. Downstream effects on insulin secretion from pancreatic beta cells indicate that these processes are relevant to GLP-1R physiological actions and might be therapeutically targetable.
AU  - Buenaventura,T
AU  - Bitsi,S
AU  - Laughlin,WE
AU  - Burgoyne,T
AU  - Lyu,Z
AU  - Oqua,AI
AU  - Norman,H
AU  - McGlone,ER
AU  - Klymchenko,AS
AU  - Corrêa,IR
AU  - Walker,A
AU  - Inoue,A
AU  - Hanyaloglu,A
AU  - Grimes,J
AU  - Koszegi,Z
AU  - Calebiro,D
AU  - Rutter,GA
AU  - Bloom,SR
AU  - Jones,B
AU  - Tomas,A
DO  - 10.1371/journal.pbio.3000097
EP  - 40
PY  - 2019///
SN  - 1544-9173
SP  - 1
TI  - Agonist-induced membrane nanodomain clustering drives GLP-1 receptor responses in pancreatic beta cells.
T2  - PLoS Biology
UR  - http://dx.doi.org/10.1371/journal.pbio.3000097
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31430273
UR  - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000097
UR  - http://hdl.handle.net/10044/1/73054
VL  - 17
ER  -
Download