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Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons

Dendrites require precise and timely delivery of protein substrates to distal areas to ensure the correct morphology and function of neurons. Many of these protein substrates are supplied in the form of ribonucleoprotein (RNP) complex consisting of RNA-binding proteins (RBPs) and mRNAs, which are su...

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Autores principales: Cha, In Jun, Lee, Davin, Park, Sung Soon, Chung, Chang Geon, Kim, Seung Yeon, Jo, Min Gu, Kim, Seung Yeol, Lee, Byung-Hoon, Lee, Young-Sam, Lee, Sung Bae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604024/
https://www.ncbi.nlm.nih.gov/pubmed/33115979
http://dx.doi.org/10.14348/molcells.2020.0158
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author Cha, In Jun
Lee, Davin
Park, Sung Soon
Chung, Chang Geon
Kim, Seung Yeon
Jo, Min Gu
Kim, Seung Yeol
Lee, Byung-Hoon
Lee, Young-Sam
Lee, Sung Bae
author_facet Cha, In Jun
Lee, Davin
Park, Sung Soon
Chung, Chang Geon
Kim, Seung Yeon
Jo, Min Gu
Kim, Seung Yeol
Lee, Byung-Hoon
Lee, Young-Sam
Lee, Sung Bae
author_sort Cha, In Jun
collection PubMed
description Dendrites require precise and timely delivery of protein substrates to distal areas to ensure the correct morphology and function of neurons. Many of these protein substrates are supplied in the form of ribonucleoprotein (RNP) complex consisting of RNA-binding proteins (RBPs) and mRNAs, which are subsequently translated in distal dendritic areas. It remains elusive, however, whether key RBPs supply mRNA according to local demands individually or in a coordinated manner. In this study, we investigated how Drosophila sensory neurons respond to the dysregulation of a disease-associated RBP, Ataxin-2 (ATX2), which leads to dendritic defects. We found that ATX2 plays a crucial role in spacing dendritic branches for the optimal dendritic receptive fields in Drosophila class IV dendritic arborization (C4da) neurons, where both expression level and subcellular location of ATX2 contribute significantly to this effect. We showed that translational upregulation through the expression of eukaryotic translation initiation factor 4E (eIF4E) further enhanced the ATX2-induced dendritic phenotypes. Additionally, we found that the expression level of another disease-associated RBP, fragile X mental retardation protein (FMRP), decreased in both cell bodies and dendrites when neurons were faced with aberrant upregulation of ATX2. Finally, we revealed that the PAM2 motif of ATX2, which mediates its interaction with poly(A)-binding protein (PABP), is potentially necessary for the decrease of FMRP in certain neuronal stress conditions. Collectively, our data suggest that dysregulation of RBPs triggers a compensatory regulation of other functionally-overlapping RBPs to minimize RBP dysregulation-associated aberrations that hinder neuronal homeostasis in dendrites.
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spelling pubmed-76040242020-11-03 Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons Cha, In Jun Lee, Davin Park, Sung Soon Chung, Chang Geon Kim, Seung Yeon Jo, Min Gu Kim, Seung Yeol Lee, Byung-Hoon Lee, Young-Sam Lee, Sung Bae Mol Cells Research Article Dendrites require precise and timely delivery of protein substrates to distal areas to ensure the correct morphology and function of neurons. Many of these protein substrates are supplied in the form of ribonucleoprotein (RNP) complex consisting of RNA-binding proteins (RBPs) and mRNAs, which are subsequently translated in distal dendritic areas. It remains elusive, however, whether key RBPs supply mRNA according to local demands individually or in a coordinated manner. In this study, we investigated how Drosophila sensory neurons respond to the dysregulation of a disease-associated RBP, Ataxin-2 (ATX2), which leads to dendritic defects. We found that ATX2 plays a crucial role in spacing dendritic branches for the optimal dendritic receptive fields in Drosophila class IV dendritic arborization (C4da) neurons, where both expression level and subcellular location of ATX2 contribute significantly to this effect. We showed that translational upregulation through the expression of eukaryotic translation initiation factor 4E (eIF4E) further enhanced the ATX2-induced dendritic phenotypes. Additionally, we found that the expression level of another disease-associated RBP, fragile X mental retardation protein (FMRP), decreased in both cell bodies and dendrites when neurons were faced with aberrant upregulation of ATX2. Finally, we revealed that the PAM2 motif of ATX2, which mediates its interaction with poly(A)-binding protein (PABP), is potentially necessary for the decrease of FMRP in certain neuronal stress conditions. Collectively, our data suggest that dysregulation of RBPs triggers a compensatory regulation of other functionally-overlapping RBPs to minimize RBP dysregulation-associated aberrations that hinder neuronal homeostasis in dendrites. Korean Society for Molecular and Cellular Biology 2020-10-31 2020-10-26 /pmc/articles/PMC7604024/ /pubmed/33115979 http://dx.doi.org/10.14348/molcells.2020.0158 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Research Article
Cha, In Jun
Lee, Davin
Park, Sung Soon
Chung, Chang Geon
Kim, Seung Yeon
Jo, Min Gu
Kim, Seung Yeol
Lee, Byung-Hoon
Lee, Young-Sam
Lee, Sung Bae
Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons
title Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons
title_full Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons
title_fullStr Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons
title_full_unstemmed Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons
title_short Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons
title_sort ataxin-2 dysregulation triggers a compensatory fragile x mental retardation protein decrease in drosophila c4da neurons
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604024/
https://www.ncbi.nlm.nih.gov/pubmed/33115979
http://dx.doi.org/10.14348/molcells.2020.0158
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