Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons

Dopamine can play opposing physiological roles depending on the receptor subtype. In the fruit fly Drosophila melanogaster, Dop1R1 and Dop2R encode the D1- and D2-like receptors, respectively, and are reported to oppositely regulate intracellular cAMP levels. Here, we profiled the expression and sub...

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Main Authors: Shun Hiramatsu, Kokoro Saito, Shu Kondo, Hidetaka Katow, Nobuhiro Yamagata, Chun-Fang Wu, Hiromu Tanimoto
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-01-01
Series:eLife
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Online Access:https://elifesciences.org/articles/98358
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author Shun Hiramatsu
Kokoro Saito
Shu Kondo
Hidetaka Katow
Nobuhiro Yamagata
Chun-Fang Wu
Hiromu Tanimoto
author_facet Shun Hiramatsu
Kokoro Saito
Shu Kondo
Hidetaka Katow
Nobuhiro Yamagata
Chun-Fang Wu
Hiromu Tanimoto
author_sort Shun Hiramatsu
collection DOAJ
description Dopamine can play opposing physiological roles depending on the receptor subtype. In the fruit fly Drosophila melanogaster, Dop1R1 and Dop2R encode the D1- and D2-like receptors, respectively, and are reported to oppositely regulate intracellular cAMP levels. Here, we profiled the expression and subcellular localization of endogenous Dop1R1 and Dop2R in specific cell types in the mushroom body circuit. For cell-type-specific visualization of endogenous proteins, we employed reconstitution of split-GFP tagged to the receptor proteins. We detected dopamine receptors at both presynaptic and postsynaptic sites in multiple cell types. Quantitative analysis revealed enrichment of both receptors at the presynaptic sites, with Dop2R showing a greater degree of localization than Dop1R1. The presynaptic localization of Dop1R1 and Dop2R in dopamine neurons suggests dual feedback regulation as autoreceptors. Furthermore, we discovered a starvation-dependent, bidirectional modulation of the presynaptic receptor expression in the protocerebral anterior medial (PAM) and posterior lateral 1 (PPL1) clusters, two distinct subsets of dopamine neurons, suggesting their roles in regulating appetitive behaviors. Our results highlight the significance of the co-expression of the two opposing dopamine receptors in the spatial and conditional regulation of dopamine responses in neurons.
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spelling doaj-art-49e08d21b91e4e4b9dcb1c117c67c3a72025-01-30T13:28:52ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.98358Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neuronsShun Hiramatsu0https://orcid.org/0000-0001-8318-4105Kokoro Saito1https://orcid.org/0009-0009-1845-5074Shu Kondo2https://orcid.org/0000-0002-4625-8379Hidetaka Katow3https://orcid.org/0009-0005-0449-230XNobuhiro Yamagata4https://orcid.org/0000-0003-1993-2038Chun-Fang Wu5https://orcid.org/0000-0002-4973-2021Hiromu Tanimoto6https://orcid.org/0000-0001-5880-6064Graduate School of Life Sciences, Tohoku University, Sendai, JapanGraduate School of Life Sciences, Tohoku University, Sendai, JapanDepartment of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, JapanDepartment of Cell Biology, New York University, New York, United StatesFaculty and Graduate School of Engineering Science, Akita University, Akita, JapanDepartment of Biology, University of Iowa, Iowa City, United StatesGraduate School of Life Sciences, Tohoku University, Sendai, JapanDopamine can play opposing physiological roles depending on the receptor subtype. In the fruit fly Drosophila melanogaster, Dop1R1 and Dop2R encode the D1- and D2-like receptors, respectively, and are reported to oppositely regulate intracellular cAMP levels. Here, we profiled the expression and subcellular localization of endogenous Dop1R1 and Dop2R in specific cell types in the mushroom body circuit. For cell-type-specific visualization of endogenous proteins, we employed reconstitution of split-GFP tagged to the receptor proteins. We detected dopamine receptors at both presynaptic and postsynaptic sites in multiple cell types. Quantitative analysis revealed enrichment of both receptors at the presynaptic sites, with Dop2R showing a greater degree of localization than Dop1R1. The presynaptic localization of Dop1R1 and Dop2R in dopamine neurons suggests dual feedback regulation as autoreceptors. Furthermore, we discovered a starvation-dependent, bidirectional modulation of the presynaptic receptor expression in the protocerebral anterior medial (PAM) and posterior lateral 1 (PPL1) clusters, two distinct subsets of dopamine neurons, suggesting their roles in regulating appetitive behaviors. Our results highlight the significance of the co-expression of the two opposing dopamine receptors in the spatial and conditional regulation of dopamine responses in neurons.https://elifesciences.org/articles/98358dopamine receptorsautoreceptorsDop1R1Dop2R
spellingShingle Shun Hiramatsu
Kokoro Saito
Shu Kondo
Hidetaka Katow
Nobuhiro Yamagata
Chun-Fang Wu
Hiromu Tanimoto
Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons
eLife
dopamine receptors
autoreceptors
Dop1R1
Dop2R
title Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons
title_full Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons
title_fullStr Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons
title_full_unstemmed Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons
title_short Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons
title_sort synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons
topic dopamine receptors
autoreceptors
Dop1R1
Dop2R
url https://elifesciences.org/articles/98358
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