RGD Reference Report - LRRK2 regulates synaptic vesicle endocytosis. - Rat Genome Database

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LRRK2 regulates synaptic vesicle endocytosis.

Authors: Shin, Narae  Jeong, Hyerhan  Kwon, Jungsun  Heo, Hye Young  Kwon, Jung June  Yun, Hye Jin  Kim, Cy-Hyun  Han, Baek Soo  Tong, Youren  Shen, Jie  Hatano, Taku  Hattori, Nobutaka  Kim, Kwang-Soo  Chang, Sunghoe  Seol, Wongi 
Citation: Shin N, etal., Exp Cell Res. 2008 Jun 10;314(10):2055-65. doi: 10.1016/j.yexcr.2008.02.015. Epub 2008 Mar 5.
RGD ID: 13462049
Pubmed: (View Article at PubMed) PMID:18445495
DOI: Full-text: DOI:10.1016/j.yexcr.2008.02.015

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.


Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Lrrk2  (leucine-rich repeat kinase 2)

Additional Information