LRRK2 在秀丽隐杆线虫中对自噬的调节。
Regulation of autophagy by LRRK2 in Caenorhabditis elegans.
机构信息
Departments of Pharmacology and Neurology, Boston University School of Medicine, Boston, Mass., USA.
出版信息
Neurodegener Dis. 2014;13(2-3):110-3. doi: 10.1159/000355654. Epub 2013 Oct 31.
Abstract
BACKGROUND
Mutations in LRRK2 (leucine-rich repeat kinase 2) are a common cause of familial Parkinson's disease. However, the mechanisms through which LRRK2 mutations contribute to neurodegeneration are poorly understood.
OBJECTIVE
We investigated the effects of WT, G2019S (GS), R1441C (RC) and kinase dead LRRK2 across multiple different cellular compartments in order to gain insight into the breadth of LRRK2 effects on cellular function.
METHODS
Nematodes expressing lgg-1::RFP, hsp1::GFP, hsp4::GFP and hsp6::GFP were crossed to nematode lines expressing WT, GS, RC or kinase dead LRRK2.
RESULTS
We observed that GS and RC LRRK2 inhibited autophagy, while WT, GS and RC LRRK2 increased the response of the mitochondrial hsp6 reporter to stress. The response of the hsp reporters under basal conditions was more nuanced.
CONCLUSION
These results support a putative role of LRRK2 in the autophagic and mitochondrial systems.
摘要
背景
LRRK2（富含亮氨酸重复激酶 2）突变是家族性帕金森病的常见原因。然而，LRRK2 突变导致神经退行性变的机制尚不清楚。
目的
我们研究了 WT、G2019S（GS）、R1441C（RC）和激酶失活 LRRK2 在多个不同细胞区室中的作用，以深入了解 LRRK2 对细胞功能的广泛影响。
方法
表达 lgg-1::RFP、hsp1::GFP、hsp4::GFP 和 hsp6::GFP 的线虫与表达 WT、GS、RC 或激酶失活 LRRK2 的线虫系杂交。
结果
我们观察到 GS 和 RC LRRK2 抑制自噬，而 WT、GS 和 RC LRRK2 增加了线粒体 hsp6 报告基因对应激的反应。基础条件下 hsp 报告基因的反应更加复杂。
结论
这些结果支持 LRRK2 在自噬和线粒体系统中的潜在作用。
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本文引用的文献
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Nat Neurosci. 2013 Apr;16(4):394-406. doi: 10.1038/nn.3350. Epub 2013 Mar 3.
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8
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PLoS One. 2011;6(8):e22354. doi: 10.1371/journal.pone.0022354. Epub 2011 Aug 3.
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