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Neurodegener Dis. 2014;13(2-3):110-3. doi: 10.1159/000355654. Epub 2013 Oct 31.

Regulation of autophagy by LRRK2 in Caenorhabditis elegans.

Author information

1
Departments of Pharmacology and Neurology, Boston University School of Medicine, Boston, Mass., USA.

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.

PMID:
24192129
PMCID:
PMC3946265
DOI:
10.1159/000355654
[Indexed for MEDLINE]
Free PMC Article

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