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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.
DGIST Authors
Chung, C.G.; Kwon, M.J.; Jeon, K.H.; Han, M.H.; Park, J.H.; Cha, I.J.; Cho, J.H.; Kim, K.; Kim, G.R.; Kim, K.; Lee, S.B.
Issue Date
2017
Citation
Cell Reports, 20(2), 356-369
Type
Article
Article Type
Article
Keywords
Ataxin 3Creb Binding Protein (CBP)CREB3L1CrebADendritesGolgi OutpostsNeurodegenerationNuclear ProteotoxicityPolyQ
ISSN
2211-1247
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://hdl.handle.net/20.500.11750/4277
DOI
10.1016/j.celrep.2017.06.059
Publisher
Elsevier B.V.
Related Researcher
  • Author Lee, Sung Bae SB LAB(Lab of Neurodegenerative diseases and Aging)
  • Research Interests Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
Files:
Collection:
Brain and Cognitive SciencesETC1. Journal Articles
New BiologyCBRG(Complex Biology Research Group)1. Journal Articles
Well Aging Research Center1. Journal Articles


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