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LRRK2 regulates synaptic vesicle endocytosis.

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.

Pubmed ID: 18445495


  • Shin N
  • Jeong H
  • Kwon J
  • Heo HY
  • Kwon JJ
  • Yun HJ
  • Kim CH
  • Han BS
  • Tong Y
  • Shen J
  • Hatano T
  • Hattori N
  • Kim KS
  • Chang S
  • Seol W


Experimental cell research

Publication Data

June 10, 2008

Associated Grants

  • Agency: NIDCD NIH HHS, Id: DC006501
  • Agency: NIMH NIH HHS, Id: MH48866
  • Agency: NINDS NIH HHS, Id: P50 NS038375

Mesh Terms

  • Animals
  • Cell Line
  • Endocytosis
  • Exocytosis
  • Humans
  • Neurons
  • Parkinson Disease
  • Protein-Serine-Threonine Kinases
  • Rats
  • Synapses
  • Synaptic Vesicles
  • Two-Hybrid System Techniques
  • rab5 GTP-Binding Proteins