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Cited 4 time in webofscience Cited 5 time in scopus
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Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons

Title
Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons
Authors
Chung, C.G.Kwon, M.J.Jeon, K.H.Hyeon, D.Y.Han, M.H.Park, J.H.Cha, I.J.Cho, J.H.Kim, K.Rho, S.Kim, G.R.Jeong, H.Lee, J.W.Kim, T.Kim, K.Kim, K.P.Ehlers, M.D.Hwang, D.Lee, S.B.
Date Issued
Jul-2017
Publisher
Cell Press
Abstract
Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis. Transcription factor enrichment analysis identified CREB3L1/CrebA, which regulates COPII gene expression. CrebA overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP synthesis, and PM supply. Chromatin immunoprecipitation (ChIP)-PCR revealed that CrebA expression is regulated by CREB-binding protein (CBP), which is sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restores the polyQ-induced dendrite pathology. Collectively, our results suggest that GOPs impaired by polyQ proteins contribute to dendrite pathology through the CBP-CrebA-COPII pathway. ? 2017 The Author(s)
URI
http://oasis.postech.ac.kr/handle/2014.oak/92070
ISSN
2211-1247
Article Type
Article
Citation
Cell Reports, vol. 20, no. 2, page. 356 - 369, 2017-07
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 HWANG, DAEHEE
Div of Integrative Biosci & Biotech
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