%0 Journal Article
%T Optical control of cell-surface and endomembrane-exclusive β-adrenergic receptor signaling.
%A Thotamune W
%A Ubeysinghe S
%A Shrestha KK
%A Mostafa ME
%A Young MC
%A Karunarathne A
%J J Biol Chem
%V 300
%N 7
%D 2024 Jul 18
%M 38901558
暂无%R 10.1016/j.jbc.2024.107481
%X Beta-adrenergic receptors (βARs) are G protein-coupled receptors (GPCRs) that mediate catecholamine hormone-induced stress responses, such as elevation of heart rate. Besides those that are plasma membrane-bound, endomembrane βARs are also signaling competent. Dysregulation of βAR pathways underlies severe pathological conditions. Emerging evidence indicates pathological molecular signatures in deeper endomembrane βARs signaling, likely contributing to conditions such as cardiomyocyte hypertrophy and apoptosis. However, the lack of approaches to control endomembrane β1ARs has impeded linking signaling with pathology. Informed by the β1AR-catecholamine interactions, we engineered an efficient photolabile proligand (OptoIso) to trigger βAR signaling exclusively in endomembrane regions using blue light stimulation. Not only does OptoIso undergo blue light deprotection in seconds, but also efficiently enters cells and allows examination of G protein heterotrimer activation exclusively at endomembranes. OptoIso also allows optical activation of plasma membrane βAR signaling in selected single cells with native fidelity, which can be reversed by terminating blue light. Thus, OptoIso will be a valuable experimental tool to elicit spatial and temporal control of βAR signaling in user-defined endomembrane or plasma membrane regions in unmodified cells with native fidelity.