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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 870 - 879 (10page)
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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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참고문헌 (34)
참고문헌 신청
Ashley, C.T., Jr. / 1993 / FMR1protein : conserved RNP family domains and selective RNA binding / Science 262:563~566
Bakthavachalu, B. / 2018 / RNP-granule assembly via Ataxin-2 disordered domains is required for long-term memory and neurodegeneration / Neuron 98:754~766
Conlon, E. G. / 2017 / RNA-binding proteins in neurodegeneration : mechanisms in aggregate / Genes Dev 31:1509~1528
Ding, D. / 2016 / ATXN2 polymorphism modulates age at onset in Machado-Joseph disease / Brain 139:e59
Eberhart, D. E. / 1996 / The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals / Hum. Mol. Genet 5:1083~1091
Bakthavachalu, B. / 2018 / RNP-granule assembly via Ataxin-2 disordered domains is required for long-term memory and neurodegeneration / Neuron 98:754~766
Conlon, E. G. / 2017 / RNA-binding proteins in neurodegeneration : mechanisms in aggregate / Genes Dev 31:1509~1528
Ding, D. / 2016 / ATXN2 polymorphism modulates age at onset in Machado-Joseph disease / Brain 139:e59
Eberhart, D. E. / 1996 / The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals / Hum. Mol. Genet 5:1083~1091
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