Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neuronsopen access
- Authors
- Chung, Chang Geon; Kwon, Min Jee; Jeon, Keun Hye; Hyeon, Do Young; Han, Myeong Hoon; Park, Jeong Hyang; Cha, In Jun; Cho, Jae Ho; Kim, Kunhyung; Rho, Sangchul; Kim, Gyu Ree; Jeong, Hyobin; Lee, Jae Won; Kim, TaeSoo; Kim, Keetae; Kim, Kwang Pyo; Ehlers, Michael D.; Hwang, Daehee; Lee, Sung Bae
- Issue Date
- Jul-2017
- Publisher
- CELL PRESS
- Citation
- CELL REPORTS, v.20, no.2, pp.356 - 369
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL REPORTS
- Volume
- 20
- Number
- 2
- Start Page
- 356
- End Page
- 369
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/193053
- DOI
- 10.1016/j.celrep.2017.06.059
- ISSN
- 2211-1247
- 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.
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