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LRRK2 regulates synaptic vesicle endocytosis |
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| 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 |
| Affiliation: | a Department of Life Science, GIST, Buk-gu, Gwangju, South Korea b Institute for Brain Science and Technology, Inje University, Gaegumdong, Busanjingu, Busan, South Korea c Graduate Program in Neuroscience, Inje University, Gaegumdong, Busanjingu, Busan, South Korea d Center for Neurologic Disease, Brigham and Women's Hospital, Boston, MA, USA e Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan f Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA, USA |
| Abstract: | 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. |
| Keywords: | Leucine-rich repeat kinase 2 Rab5b Endocytosis Parkinson's disease Synaptic vesicles |
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