KMID : 0578320200430100870
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Molecules and Cells 2020 Volume.43 No. 10 p.870 ~ p.879
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Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons
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Cha In-Jun
Lee Da-Vin Park Sung-Soon Chung Chang-Geon Kim Seung-Yeon Jo Min-Gu Kim Seung-Yeol Lee Byung-Hoon Lee Young-Sam Lee Sung-Bae
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Abstract
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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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KEYWORD
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Ataxin-2, dendrite, fragile X mental retardation protein, mRNA supply, RNA-binding protein
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