期刊
EXPERIMENTAL CELL RESEARCH
卷 314, 期 10, 页码 2055-2065出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2008.02.015
关键词
leucine-rich repeat kinase 2; Rab5b; endocytosis; Parkinson's disease; synaptic vesicles
资金
- NIDCD NIH HHS [DC006501] Funding Source: Medline
- NIMH NIH HHS [MH48866] Funding Source: Medline
- NINDS NIH HHS [P50 NS038375, R37 NS071251] Funding Source: Medline
- Ministry of Education, Science & Technology (MoST), Republic of Korea [2007-00237] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [과06A1202, 2006-311-C00512] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The leucine-rich repeat kinase 2 (LRRK2) has been identified as the defective gene at the PARK8 locus causing the autosomal dominant form of Parkinson's disease (PD). Although several LRRK2 mutations were found in familial as well as sporadic PD patients, its physiological functions are not clearly defined. In this study, using yeast two-hybrid screening, we report the identification of Rab5b as an LRRK2-interacting protein. Indeed, our GST pull down and co-immunoprecipitation assays showed that it specifically interacts with LRRK2. In addition, subcellular fractionation and immunocytochemical analyses confirmed that a fraction of both proteins co-localize in synaptic vesicles. Interestingly, we found that alteration of LRRK2 expression by either overexpression or knockdown of endogenous LRRK2 in primary neuronal cells significantly impairs synaptic vesicle endocytosis. Furthermore, this endocytosis defect was rescued by co-expression of functional Rab5b protein, but not by its inactive form. Taken together, we propose that LRRK2, in conjunction with its interaction with Rab5b, plays an important role in synaptic function by modulating the endocytosis of synaptic vesicles. (c) 2008 Elsevier Inc. All rights reserved.
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