Molecules and Cells

  • 제43권10호
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  • Pages.870-879
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  • 2020
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons

  • Cha, In Jun (Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST)) ;
  • Lee, Davin (Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST)) ;
  • Park, Sung Soon (Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST)) ;
  • Chung, Chang Geon (Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST)) ;
  • Kim, Seung Yeon (Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST)) ;
  • Jo, Min Gu (Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST)) ;
  • Kim, Seung Yeol (Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST)) ;
  • Lee, Byung-Hoon (Protein Dynamics-Based Proteotoxicity Control Laboratory, Basic Research Lab, DGIST) ;
  • Lee, Young-Sam (Protein Dynamics-Based Proteotoxicity Control Laboratory, Basic Research Lab, DGIST) ;
  • Lee, Sung Bae (Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST))
  • 투고 : 2020.07.24
  • 심사 : 2020.09.24
  • 발행 : 2020.10.31
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초록

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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참고문헌

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피인용 문헌

  1. RNA Modifications and RNA Metabolism in Neurological Disease Pathogenesis vol.22, pp.21, 2020, https://doi.org/10.3390/ijms222111870