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PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III

Dopamine neurons are essential for voluntary movement, reward learning, and motivation, and their dysfunction is closely linked to various psychological and neurodegenerative diseases. Hence, understanding the detailed signaling mechanisms that functionally modulate dopamine neurons is crucial for t...

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Autores principales: Kim, Hye Yun, Lee, Jieun, Kim, Hyun-Jin, Lee, Byeong Eun, Jeong, Jaewook, Cho, Eun Jeong, Jang, Hyun-Jun, Shin, Kyeong Jin, Kim, Min Ji, Chae, Young Chan, Lee, Seung Eun, Myung, Kyungjae, Baik, Ja-Hyun, Suh, Pann-Ghill, Kim, Jae-Ick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10689754/
https://www.ncbi.nlm.nih.gov/pubmed/37907739
http://dx.doi.org/10.1038/s12276-023-01104-y
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author Kim, Hye Yun
Lee, Jieun
Kim, Hyun-Jin
Lee, Byeong Eun
Jeong, Jaewook
Cho, Eun Jeong
Jang, Hyun-Jun
Shin, Kyeong Jin
Kim, Min Ji
Chae, Young Chan
Lee, Seung Eun
Myung, Kyungjae
Baik, Ja-Hyun
Suh, Pann-Ghill
Kim, Jae-Ick
author_facet Kim, Hye Yun
Lee, Jieun
Kim, Hyun-Jin
Lee, Byeong Eun
Jeong, Jaewook
Cho, Eun Jeong
Jang, Hyun-Jun
Shin, Kyeong Jin
Kim, Min Ji
Chae, Young Chan
Lee, Seung Eun
Myung, Kyungjae
Baik, Ja-Hyun
Suh, Pann-Ghill
Kim, Jae-Ick
author_sort Kim, Hye Yun
collection PubMed
description Dopamine neurons are essential for voluntary movement, reward learning, and motivation, and their dysfunction is closely linked to various psychological and neurodegenerative diseases. Hence, understanding the detailed signaling mechanisms that functionally modulate dopamine neurons is crucial for the development of better therapeutic strategies against dopamine-related disorders. Phospholipase Cγ1 (PLCγ1) is a key enzyme in intracellular signaling that regulates diverse neuronal functions in the brain. It was proposed that PLCγ1 is implicated in the development of dopaminergic neurons, while the physiological function of PLCγ1 remains to be determined. In this study, we investigated the physiological role of PLCγ1, one of the key effector enzymes in intracellular signaling, in regulating dopaminergic function in vivo. We found that cell type-specific deletion of PLCγ1 does not adversely affect the development and cellular morphology of midbrain dopamine neurons but does facilitate dopamine release from dopaminergic axon terminals in the striatum. The enhancement of dopamine release was accompanied by increased colocalization of vesicular monoamine transporter 2 (VMAT2) at dopaminergic axon terminals. Notably, dopamine neuron-specific knockout of PLCγ1 also led to heightened expression and colocalization of synapsin III, which controls the trafficking of synaptic vesicles. Furthermore, the knockdown of VMAT2 and synapsin III in dopamine neurons resulted in a significant attenuation of dopamine release, while this attenuation was less severe in PLCγ1 cKO mice. Our findings suggest that PLCγ1 in dopamine neurons could critically modulate dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III.
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spelling pubmed-106897542023-12-02 PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III Kim, Hye Yun Lee, Jieun Kim, Hyun-Jin Lee, Byeong Eun Jeong, Jaewook Cho, Eun Jeong Jang, Hyun-Jun Shin, Kyeong Jin Kim, Min Ji Chae, Young Chan Lee, Seung Eun Myung, Kyungjae Baik, Ja-Hyun Suh, Pann-Ghill Kim, Jae-Ick Exp Mol Med Article Dopamine neurons are essential for voluntary movement, reward learning, and motivation, and their dysfunction is closely linked to various psychological and neurodegenerative diseases. Hence, understanding the detailed signaling mechanisms that functionally modulate dopamine neurons is crucial for the development of better therapeutic strategies against dopamine-related disorders. Phospholipase Cγ1 (PLCγ1) is a key enzyme in intracellular signaling that regulates diverse neuronal functions in the brain. It was proposed that PLCγ1 is implicated in the development of dopaminergic neurons, while the physiological function of PLCγ1 remains to be determined. In this study, we investigated the physiological role of PLCγ1, one of the key effector enzymes in intracellular signaling, in regulating dopaminergic function in vivo. We found that cell type-specific deletion of PLCγ1 does not adversely affect the development and cellular morphology of midbrain dopamine neurons but does facilitate dopamine release from dopaminergic axon terminals in the striatum. The enhancement of dopamine release was accompanied by increased colocalization of vesicular monoamine transporter 2 (VMAT2) at dopaminergic axon terminals. Notably, dopamine neuron-specific knockout of PLCγ1 also led to heightened expression and colocalization of synapsin III, which controls the trafficking of synaptic vesicles. Furthermore, the knockdown of VMAT2 and synapsin III in dopamine neurons resulted in a significant attenuation of dopamine release, while this attenuation was less severe in PLCγ1 cKO mice. Our findings suggest that PLCγ1 in dopamine neurons could critically modulate dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III. Nature Publishing Group UK 2023-11-01 /pmc/articles/PMC10689754/ /pubmed/37907739 http://dx.doi.org/10.1038/s12276-023-01104-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kim, Hye Yun
Lee, Jieun
Kim, Hyun-Jin
Lee, Byeong Eun
Jeong, Jaewook
Cho, Eun Jeong
Jang, Hyun-Jun
Shin, Kyeong Jin
Kim, Min Ji
Chae, Young Chan
Lee, Seung Eun
Myung, Kyungjae
Baik, Ja-Hyun
Suh, Pann-Ghill
Kim, Jae-Ick
PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III
title PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III
title_full PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III
title_fullStr PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III
title_full_unstemmed PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III
title_short PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III
title_sort plcγ1 in dopamine neurons critically regulates striatal dopamine release via vmat2 and synapsin iii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10689754/
https://www.ncbi.nlm.nih.gov/pubmed/37907739
http://dx.doi.org/10.1038/s12276-023-01104-y
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