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: PMID:18445495   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yexcr.2008.02.015   (Journal Full-text)

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.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Lrrk2Ratpositive regulation of synaptic vesicle endocytosis  IMP  RGD 

Cellular Component

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Lrrk2Ratneuronal cell body  IDA  RGD 
Lrrk2Ratpresynaptic cytosol is_active_inIDA PMID:18445495SynGO 
Lrrk2Ratpresynaptic cytosol is_active_inIEP PMID:18445495SynGO 


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