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Widespread posttranscriptional regulation of cotransmission

While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters...

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Autores principales: Chen, Nannan, Zhang, Yunpeng, Rivera-Rodriguez, Emmanuel J., Yu, Albert D., Hobin, Michael, Rosbash, Michael, Griffith, Leslie C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413644/
https://www.ncbi.nlm.nih.gov/pubmed/37267358
http://dx.doi.org/10.1126/sciadv.adg9836
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author Chen, Nannan
Zhang, Yunpeng
Rivera-Rodriguez, Emmanuel J.
Yu, Albert D.
Hobin, Michael
Rosbash, Michael
Griffith, Leslie C.
author_facet Chen, Nannan
Zhang, Yunpeng
Rivera-Rodriguez, Emmanuel J.
Yu, Albert D.
Hobin, Michael
Rosbash, Michael
Griffith, Leslie C.
author_sort Chen, Nannan
collection PubMed
description While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in Drosophila. We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a “translation-trap” strategy, we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of cotransmission is actively modulated. Posttranscriptional restriction of fast transmitter cotransmission provides a mechanism allowing reversible tuning of neuronal output.
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spelling pubmed-104136442023-08-11 Widespread posttranscriptional regulation of cotransmission Chen, Nannan Zhang, Yunpeng Rivera-Rodriguez, Emmanuel J. Yu, Albert D. Hobin, Michael Rosbash, Michael Griffith, Leslie C. Sci Adv Neuroscience While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in Drosophila. We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a “translation-trap” strategy, we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of cotransmission is actively modulated. Posttranscriptional restriction of fast transmitter cotransmission provides a mechanism allowing reversible tuning of neuronal output. American Association for the Advancement of Science 2023-06-02 /pmc/articles/PMC10413644/ /pubmed/37267358 http://dx.doi.org/10.1126/sciadv.adg9836 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Neuroscience
Chen, Nannan
Zhang, Yunpeng
Rivera-Rodriguez, Emmanuel J.
Yu, Albert D.
Hobin, Michael
Rosbash, Michael
Griffith, Leslie C.
Widespread posttranscriptional regulation of cotransmission
title Widespread posttranscriptional regulation of cotransmission
title_full Widespread posttranscriptional regulation of cotransmission
title_fullStr Widespread posttranscriptional regulation of cotransmission
title_full_unstemmed Widespread posttranscriptional regulation of cotransmission
title_short Widespread posttranscriptional regulation of cotransmission
title_sort widespread posttranscriptional regulation of cotransmission
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413644/
https://www.ncbi.nlm.nih.gov/pubmed/37267358
http://dx.doi.org/10.1126/sciadv.adg9836
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