Optimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors

Fangmin Zhou, Alexandra-Madelaine Tichy, Bibi Nusreen Imambocus, Shreyas Sakharwade, Francisco J. Rodriguez Jimenez, Marco González Martínez, Ishrat Jahan, Margarita Habib, Nina Wilhelmy, Vanessa Burre, Tatjana Lömker, Kathrin Sauter, Charlotte Helfrich-Förster, Jan Pielage, Ilona C. Grunwald Kadow, Harald Janovjak and Peter Soba ()
Additional contact information
Fangmin Zhou: Friedrich-Alexander-Universität Erlangen-Nürnberg
Alexandra-Madelaine Tichy: Monash University
Bibi Nusreen Imambocus: University of Bonn
Shreyas Sakharwade: Friedrich-Alexander-Universität Erlangen-Nürnberg
Francisco J. Rodriguez Jimenez: University Clinic Bonn (UKB), University of Bonn
Marco González Martínez: University Clinic Bonn (UKB), University of Bonn
Ishrat Jahan: University Clinic Bonn (UKB), University of Bonn
Margarita Habib: Biocenter, University of Würzburg
Nina Wilhelmy: RPTU University of Kaiserslautern
Vanessa Burre: RPTU University of Kaiserslautern
Tatjana Lömker: University Medical Center Hamburg-Eppendorf
Kathrin Sauter: University Medical Center Hamburg-Eppendorf
Charlotte Helfrich-Förster: Biocenter, University of Würzburg
Jan Pielage: RPTU University of Kaiserslautern
Ilona C. Grunwald Kadow: University Clinic Bonn (UKB), University of Bonn
Harald Janovjak: Monash University
Peter Soba: Friedrich-Alexander-Universität Erlangen-Nürnberg

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Neuromodulatory signaling via G protein-coupled receptors (GPCRs) plays a pivotal role in regulating neural network function and animal behavior. The recent development of optogenetic tools to induce G protein-mediated signaling provides the promise of acute and cell type-specific manipulation of neuromodulatory signals. However, designing and deploying optogenetically functionalized GPCRs (optoXRs) with accurate specificity and activity to mimic endogenous signaling in vivo remains challenging. Here we optimize the design of optoXRs by considering evolutionary conserved GPCR-G protein interactions and demonstrate the feasibility of this approach using two Drosophila Dopamine receptors (optoDopRs). These optoDopRs exhibit high signaling specificity and light sensitivity in vitro. In vivo, we show receptor and cell type-specific effects of dopaminergic signaling in various behaviors, including the ability of optoDopRs to rescue the loss of the endogenous receptors. This work demonstrates that optoXRs can enable optical control of neuromodulatory receptor-specific signaling in functional and behavioral studies.

Date: 2023
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DOI: 10.1038/s41467-023-43970-0

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