Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease.
Proc Natl Acad Sci U S A
; 111(7): 2626-31, 2014 Feb 18.
Article
em En
| MEDLINE
| ID: mdl-24510904
ABSTRACT
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein-protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G-associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy-lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Proteínas Serina-Treonina Quinases
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Predisposição Genética para Doença
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Mapeamento de Interação de Proteínas
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Complexos Multiproteicos
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Loci Gênicos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article