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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.; Kim, K.P.; Ehlers, M.D.; Hwang, D.; Lee, S.B.
- DGIST Authors
- Kim, K.; Lee, S.B.
- Issue Date
- Cell Reports, 20(2), 356-369
- Article Type
- Ataxin 3; Creb Binding Protein (CBP); CREB3L1; CrebA; Dendrites; Golgi Outposts; Neurodegeneration; Nuclear Proteotoxicity; PolyQ
- 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)
- Elsevier B.V.
- Related Researcher
Laboratory of Neurodegenerative Diseases and Aging
Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
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- Department of New BiologyCBRG(Complex Biology Research Group)1. Journal Articles
Department of Brain and Cognitive SciencesLaboratory of Neurodegenerative Diseases and Aging1. Journal Articles
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