Optimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors
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Optimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors. / Zhou, Fangmin; Tichy, Alexandra-Madelaine; Imambocus, Bibi Nusreen; Sakharwade, Shreyas; Rodriguez Jimenez, Francisco J; González Martínez, Marco; Jahan, Ishrat; Habib, Margarita; Wilhelmy, Nina; Burre, Vanessa; Lömker, Tatjana; Sauter, Kathrin; Helfrich-Förster, Charlotte; Pielage, Jan; Grunwald Kadow, Ilona C; Janovjak, Harald; Soba, Peter.
In: NAT COMMUN, Vol. 14, No. 1, 19.12.2023, p. 8434.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Optimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors
AU - Zhou, Fangmin
AU - Tichy, Alexandra-Madelaine
AU - Imambocus, Bibi Nusreen
AU - Sakharwade, Shreyas
AU - Rodriguez Jimenez, Francisco J
AU - González Martínez, Marco
AU - Jahan, Ishrat
AU - Habib, Margarita
AU - Wilhelmy, Nina
AU - Burre, Vanessa
AU - Lömker, Tatjana
AU - Sauter, Kathrin
AU - Helfrich-Förster, Charlotte
AU - Pielage, Jan
AU - Grunwald Kadow, Ilona C
AU - Janovjak, Harald
AU - Soba, Peter
N1 - © 2023. The Author(s).
PY - 2023/12/19
Y1 - 2023/12/19
N2 - 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.
AB - 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.
KW - Animals
KW - Receptors, Dopamine/genetics
KW - Receptors, G-Protein-Coupled/metabolism
KW - Signal Transduction
KW - GTP-Binding Proteins/metabolism
KW - Drosophila/genetics
U2 - 10.1038/s41467-023-43970-0
DO - 10.1038/s41467-023-43970-0
M3 - SCORING: Journal article
C2 - 38114457
VL - 14
SP - 8434
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -