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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.P.Ehlers M.D.Hwang D.Lee S.B.
Ewha Authors
김태수
SCOPUS Author ID
김태수scopus
Issue Date
2017
Journal Title
Cell Reports
ISSN
2211-1247JCR Link
Citation
vol. 20, no. 2, pp. 356 - 369
Keywords
ataxin-3CBPCREB3L1CrebAdendritesGolgi outpostsneurodegenerationnuclear proteotoxicitypolyQ
Publisher
Elsevier B.V.
Indexed
SCIE; SCOPUS WOS scopus
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)
DOI
10.1016/j.celrep.2017.06.059
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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