Drosophila melanogaster
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA274298 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1784890_1.fastq.gz | Fastqsanger.gz | |||
| SRR1784890_2.fastq.gz | Fastqsanger.gz | |||
| SRR1784887_1.fastq.gz | Fastqsanger.gz | |||
| SRR1784887_2.fastq.gz | Fastqsanger.gz | |||
| SRR1784888_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
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Project description: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 with a loss of Golgi outposts (GOPs) and decreased supply of plasma membrane (PM) in Drosophila Class IV da (C4da) neurons. mRNA sequencing revealed that down-regulated genes 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 C4da neurons restored the dysregulation of COPII genes, GOP synthesis, and PM supply. The ChIP-PCR assay revealed that CrebA expression was regulated by CBP, which was sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restored 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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Project description:Recycling and supply of plasma membrane (PM), referred to as PM turnover, are essential for maintaining integrity of neurons undergoing continuous dynamic morphological changes. Yet, the link of PM turnover to neuronal pathophysiology remains largely elusive. Here we showed that a subset of toxic polyglutamine proteins markedly compromised local targeting-recycling of PM components, reflecting a unique feature of early neuropathies. Such disruption of PM turnover in dendrites was ascribed primarily to alterations in dendritic endosomes and Golgi outposts accounting for local PM recycling and supply, respectively. Genome-wide mRNA-sequencing analysis identified CREB3L1/CrebA-COPII pathway to be responsible for the disruption of PM turnover. Indeed, CrebA overexpression reversed PM turnover impairment caused by these toxic proteins through restoring COPII pathway. Thus we demonstrate how PM turnover is linked to aberration of neuronal integrity in pathological conditions as well as its near-complete restoration through genetic engineering of CREB3L1/CrebA-COPII pathway.
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