Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Poster Abstracts

11-POS Board 11 THE EFFECTS OF GRK2 ON GPR75 TRAFFICKING AND PLASMA MEMBRANE EXPRESSION Teodora Stratulat 1,2 ; Rodica Badea 1 ; Aura-Elena Ionescu 1 ; Alexandru Babes 2 ; Sorin Tunaru 1 ; 1 Institute of Biochemistry of the Romanian Academy, Cell Signaling Research Group, Bucharest, Romania 2 Faculty of Biology, University of Bucharest, Department of Anatomy, Physiology and Biophysics, Bucharest, Romania G protein-coupled receptor 75 (GPR75), currently classified as an orphan receptor with an emerging pharmacology [1], has garnered a lot of attention for its roles in metabolic disorders [2], cardiovascular function [3], and other pathologies. G protein receptor kinase 2 (GRK2) is a serine-threonine kinase canonically described to phosphorylate active GPCRs, leading to β -arrestin coupling, desensitization and internalization [4].Methods: We used immunoblotting to determine receptor expression and glycosylation status, and whole-cell ELISA to look at expression levels at the plasma membrane. Results: We show that GRK2, and the closely related GRK3, lead to a marked decrease in the receptor’s plasma membrane expression levels and intracellular sequestration. We report a new GRK2-induced glycosylated form of the receptor. All these effects depend on the catalytic activity of the kinase (shown by using a dominant negative GRK2).Conclusions: GRKs may modulate the activity and trafficking of receptors that are not ligand-bound or active, supporting the existence of a novel mechanism of receptor regulation, which could be relevant considering the emerging pharmacology and physiological functions of GPR75.Bibliography1. Alexander SPH, Battey J, Benson HE, et al (2023) Class A Orphans in GtoPdb v.2023.1. IUPHAR/BPS Guide to Pharmacology CITE 2023.2. Akbari P, Gilani A, Sosina O, et al (2021) Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity. Science (1979) 373.3. Garcia V, Gilani A, Shkolnik B, et al (2017) 20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (Gq) to Affect Vascular Function and Trigger Hypertension. Circ Res 120:1776– 1788.4. Gurevich V V., Gurevich E V. (2019) GPCR Signaling Regulation: The Role of GRKs and Arrestins. Front Pharmacol 10. AcknowledgementsThis work was funded by an EEA Romania-Norway research grant (2018-0535) entitled ‘New Generation of Drug Targets for Schizophrenia’, (NEXTDRUG).

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