Spatiotemporally resolved GPCR interactome uncovers unique mediators of receptor agonism
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2025-05-15
Date Acceptance
2025-04-14
Citation
Cell Chemical Biology, 2025, 32 (5), pp.722-735.e7
ISSN
2451-9448
Publisher
Cell Press
Start Page
722
End Page
735.e7
Journal / Book Title
Cell Chemical Biology
Volume
32
Issue
5
Copyright Statement
© 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.chembiol.2025.04.006
Publication Status
Published
Date Publish Online
2025-05-15