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Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons

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Title
Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons
Author(s)
Chang Geon Chung; Min Jee Kwon; Keun Hye Jeon; Do Young Hyeon; Myeong Hoon Han; Jeong Hyang Park; In Jun Cha; Jae Ho Cho; Kunhyung Kim; Sangchul Rho; Gyu Ree Kim; Hyobin Jeong; Jae Won Lee; TaeSoo Kim; Keetae Kim; Kwang Pyo Kim; Michael D. Ehlers; Daehee Hwang; Sung Bae Lee
Publication Date
2017-07
Journal
CELL REPORTS, v.20, no.2, pp.356 - 369
Publisher
CELL PRESS
Abstract
Dendrite aberration is a common feature of neurode-generative 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. (c) 2017 The Author(s).
URI
https://pr.ibs.re.kr/handle/8788114/3651
DOI
10.1016/j.celrep.2017.06.059
ISSN
2211-1247
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > 1. Journal Papers (저널논문)
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13.Cell_Reports_2017_Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons.pdfDownload

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