View : 8 Download: 0
Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons
- Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons
- 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.P.; Ehlers M.D.; Hwang D.; Lee S.B.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Cell Reports
- vol. 20, no. 2, pp. 356 - 369
- ataxin-3; CBP; CREB3L1; CrebA; dendrites; Golgi outposts; neurodegeneration; nuclear proteotoxicity; polyQ
- Elsevier B.V.
- SCIE; SCOPUS
- 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)
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
- Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.