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@article{Shchepinova:2025:10.1016/j.chembiol.2025.04.006,
author = {Shchepinova, MM and Richardson, R and Houghton, JW and Walker, AR and Safar, MA and Conole, D and Hanyaloglu, AC and Tate, EW},
doi = {10.1016/j.chembiol.2025.04.006},
journal = {Cell Chemical Biology},
pages = {722--735.e7},
title = {Spatiotemporally resolved GPCR interactome uncovers unique mediators of receptor agonism},
url = {http://dx.doi.org/10.1016/j.chembiol.2025.04.006},
volume = {32},
year = {2025}
}
TY - JOUR
AB - Cellular signaling by membrane G protein-coupled receptors (GPCRs) is governed by a complex and diverse array of mechanisms. The dynamics of a GPCR interactome, as it evolves over time and space in response to an agonist, provide a unique perspective on pleiotropic signaling decoding and functional selectivity at the cellular level. In this study, we utilized proximity-based APEX2 proteomics to investigate the interaction network of the luteinizing hormone receptor (LHR) on a minute-to-minute timescale. We developed an analytical approach that integrates quantitative multiplexed proteomics with temporal reference profiles, creating a platform to identify the proteomic environment of APEX2-tagged LHR at the nanometer scale. LHR activity is finely regulated spatially, leading to the identification of putative interactors, including the Ras-related GTPase RAP2B, which modulate both receptor signaling and post-endocytic trafficking. This work provides a valuable resource for spatiotemporal nanodomain mapping of LHR interactors across subcellular compartments.
AU - Shchepinova,MM
AU - Richardson,R
AU - Houghton,JW
AU - Walker,AR
AU - Safar,MA
AU - Conole,D
AU - Hanyaloglu,AC
AU - Tate,EW
DO - 10.1016/j.chembiol.2025.04.006
EP - 735
PY - 2025///
SN - 2451-9448
SP - 722
TI - Spatiotemporally resolved GPCR interactome uncovers unique mediators of receptor agonism
T2 - Cell Chemical Biology
UR - http://dx.doi.org/10.1016/j.chembiol.2025.04.006
UR - https://doi.org/10.1016/j.chembiol.2025.04.006
VL - 32
ER -
Prof. Ed Tate
GSK Chair in Chemical Biology
Department of Chemistry
Molecular Sciences Research Hub, White City Campus,
82 Wood Lane, London, W12 0BZ
e.tate@imperial.ac.uk
Tel: +44 (0)20 759 + ext 43752 or 45821