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Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics.

Published version
Peer-reviewed

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Type

Article

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Authors

Arvaniti, Anastasia 
Ashford, Fiona B 

Abstract

The glucagon-like peptide-1 receptor (GLP1R) is a class B G protein-coupled receptor (GPCR) involved in metabolism. Presently, its visualization is limited to genetic manipulation, antibody detection or the use of probes that stimulate receptor activation. Herein, we present LUXendin645, a far-red fluorescent GLP1R antagonistic peptide label. LUXendin645 produces intense and specific membrane labeling throughout live and fixed tissue. GLP1R signaling can additionally be evoked when the receptor is allosterically modulated in the presence of LUXendin645. Using LUXendin645 and LUXendin651, we describe islet, brain and hESC-derived β-like cell GLP1R expression patterns, reveal higher-order GLP1R organization including membrane nanodomains, and track single receptor subpopulations. We furthermore show that the LUXendin backbone can be optimized for intravital two-photon imaging by installing a red fluorophore. Thus, our super-resolution compatible labeling probes allow visualization of endogenous GLP1R, and provide insight into class B GPCR distribution and dynamics both in vitro and in vivo.

Description

Keywords

Amino Acid Sequence, Animals, Brain, Cell Line, Fluorescent Dyes, Glucagon-Like Peptide-1 Receptor, HEK293 Cells, Human Embryonic Stem Cells, Humans, Islets of Langerhans, Mice, Mice, Knockout, Microscopy, Fluorescence, Multiphoton, Models, Molecular, Molecular Structure, Peptide Fragments, Signal Transduction, Tissue Distribution

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12012/3)
MRC (MC_UU_00014/3)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_12012)