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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
Authors
Cha, InJunLee, DavinPark, Sung SoonChung, Chang GeonKim, Seung YeonJo, Min GuKim, SeungYeolLee, Byung-HoonLee, Young-SamLee, Sung Bae
DGIST Authors
Cha, InJun; Lee, Davin; Park, Sung Soon; Chung, Chang Geon; Kim, Seung Yeon; Jo, Min Gu; Kim, SeungYeol; Lee, Byung-HoonLee, Young-SamLee, Sung Bae
Issue Date
2020-10
Citation
Molecules and Cells, 43(10), 870-879
Type
Article
Article Type
Article
Author Keywords
Ataxin-2dendritefragile X mental retardation proteinmRNA supplyRNA-binding protein
Keywords
RNA-BINDING PROTEINSTRANSLATIONGENENEURODEGENERATIONDOMAINSTDP-43FMR1
ISSN
1016-8478
Abstract
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. © The Korean Society for Molecular and Cellular Biology. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/12670
DOI
10.14348/molcells.2020.0158
Publisher
Korean Society for Molecular and Cellular Biology
Related Researcher
  • Author Lee, Sung Bae Laboratory of Neurodegenerative Diseases and Aging
  • Research Interests Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
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Collection:
Department of New BiologyLab of Protein Homeostasis and Drug Discovery1. Journal Articles
Department of New BiologySenescence-Associated Mechanism Lab1. Journal Articles
Department of Brain and Cognitive SciencesLaboratory of Neurodegenerative Diseases and Aging1. Journal Articles


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