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Distinct Regions in the C-Terminus Required for GLP-1R Cell Surface Expression, Activity and Internalisation / Aiysha Thompson; Venkateswarlu Kanamarlapudi

Molecular and Cellular Endocrinology, Volume: 413, Pages: 66 - 77

Swansea University Author: Kanamarlapudi, Venkat

DOI (Published version): 10.1016/j.mce.2015.06.012

Abstract

The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), an important drug target in the treatment of type 2 diabetes, is a G-protein coupled receptor (GPCR) that mediates insulin secretion by GLP-1. The N-terminus controls GLP-1R biosynthetic trafficking to the cell surface but the C-terminus involve...

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Published in: Molecular and Cellular Endocrinology
Published: 2015
URI: https://cronfa.swan.ac.uk/Record/cronfa22217
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Abstract: The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), an important drug target in the treatment of type 2 diabetes, is a G-protein coupled receptor (GPCR) that mediates insulin secretion by GLP-1. The N-terminus controls GLP-1R biosynthetic trafficking to the cell surface but the C-terminus involvement in that trafficking is unknown. The aim of this study was to identify distinct regions within the C-terminal domain required for human GLP-1R (hGLP-1R) cell surface expression, activity and internalisation using a number of C-terminal deletions and site-directed mutations. The results of this study revealed that the residues 411-418 within the C-terminal domain of the hGLP-1R are critical in targeting the newly synthesised receptor to the plasma membrane. The residues 419-430 are important for cAMP producing activity of the receptor, most likely by coupling to Gαs. However, the residues 431-450 within the C-terminus are essential for agonist-induced hGLP-1R internalisation. In conclusion, these findings demonstrate the hGLP-1R has distinct regions within the C-terminal domain required for its cell surface expression, activity and agonist-induced internalisation.
Keywords: Glucagon like peptide-1 (GLP-1); GLP-1 receptor (GLP-1R); G protein coupled receptor (GPCR); Biosynthetic trafficking; C-terminus; Diabetes
College: Swansea University Medical School
Start Page: 66
End Page: 77