Regulation of Autophagy by LRRK2 in Caenorhabditis elegans
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) a...
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Published in | Neuro-degenerative diseases Vol. 13; no. 2-3; pp. 110 - 113 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Basel, Switzerland
S. Karger AG
01.01.2014
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISBN: | 9783318025118 3318025119 |
ISSN: | 1660-2854 1660-2862 |
DOI: | 10.1159/000355654 |