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Optical Control of Dopamine D2-like Receptors with Cell-Specific Fast-Relaxing Photoswitches.

ABSTRACT: Dopamine D2-like receptors (D2R, D3R, and D4R) control diverse physiological and behavioral functions and are important targets for the treatment of a variety of neuropsychiatric disorders. Their complex distribution and activation kinetics in the brain make it difficult to target specific receptor populations with sufficient precision. We describe a new toolkit of light-activatable, fast-relaxing, covalently taggable chemical photoswitches that fully activate, partially activate, or block D2-like receptors. This technology combines the spatiotemporal precision of a photoswitchable ligand (P) with cell type and spatial specificity of a genetically encoded membrane anchoring protein (M) to which the P tethers. These tools set the stage for targeting endogenous D2-like receptor signaling with molecular, cellular, and spatiotemporal precision using only one wavelength of light.

SUBMITTER: Hetzler BE

PROVIDER: S-EPMC10472511 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Optical Control of Dopamine D2-like Receptors with Cell-Specific Fast-Relaxing Photoswitches.

Hetzler Belinda E BE Donthamsetti Prashant P Peitsinis Zisis Z Stanley Cherise C Trauner Dirk D Isacoff Ehud Y EY

Journal of the American Chemical Society 20230816 34

Dopamine D2-like receptors (D2R, D3R, and D4R) control diverse physiological and behavioral functions and are important targets for the treatment of a variety of neuropsychiatric disorders. Their complex distribution and activation kinetics in the brain make it difficult to target specific receptor populations with sufficient precision. We describe a new toolkit of light-activatable, fast-relaxing, covalently taggable chemical photoswitches that fully activate, partially activate, or block D2-li ...[more]

PMID: 37586061

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