Dataset Information

In-silico predicted mouse melanopsins with blue spectral shifts deliver efficient subcellular signaling.

ABSTRACT: Melanopsin is a photopigment belonging to the G Protein-Coupled Receptor (GPCR) family expressed in a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) and responsible for a variety of processes. The bistability and, thus, the possibility to function under low retinal availability would make melanopsin a powerful optogenetic tool. Here, we aim to utilize mouse melanopsin to trigger macrophage migration by its subcellular optical activation with localized blue light, while simultaneously imaging the migration with red light. To reduce melanopsin's red light sensitivity, we employ a combination of in silico structure prediction and automated quantum mechanics/molecular mechanics modeling to predict minimally invasive mutations to shift its absorption spectrum towards the shorter wavelength region of the visible spectrum without compromising the signaling efficiency. The results demonstrate that it is possible to achieve melanopsin mutants that resist red light-induced activation but are activated by blue light and display properties indicating preserved bistability. Using the A333T mutant, we show that the blue light-induced subcellular melanopsin activation triggers localized PIP3 generation and macrophage migration, which we imaged using red light, demonstrating the optogenetic utility of minimally engineered melanopsins.

SUBMITTER: Wijayaratna D

PROVIDER: S-EPMC11312219 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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In-silico predicted mouse melanopsins with blue spectral shifts deliver efficient subcellular signaling.

Wijayaratna Dhanushan D Sacchetta Filippo F Pedraza-González Laura L Fanelli Francesca F Sugihara Tomohiro T Koyanagi Mitsumasa M Piyawardana Senuri S Ghotra Kiran K Thotamune Waruna W Terakita Akihisa A Olivucci Massimo M Karunarathne Ajith A

Cell communication and signaling : CCS 20240808 1

Melanopsin is a photopigment belonging to the G Protein-Coupled Receptor (GPCR) family expressed in a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) and responsible for a variety of processes. The bistability and, thus, the possibility to function under low retinal availability would make melanopsin a powerful optogenetic tool. Here, we aim to utilize mouse melanopsin to trigger macrophage migration by its subcellular optical activation with localized blue light, while si ...[more]

PMID: 39118111

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Dataset Information

In-silico predicted mouse melanopsins with blue spectral shifts deliver efficient subcellular signaling.

Publications

In-silico predicted mouse melanopsins with blue spectral shifts deliver efficient subcellular signaling.

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