LRRK2 regulates synaptic vesicle endocytosis.

LRRK2 regulates synaptic vesicle endocytosis. Research Abstract Details 

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LRRK2 regulates synaptic vesicle endocytosis. Abstract 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.

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LRRK2 regulates synaptic vesicle endocytosis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Experimental cell research

VOLUME: 314

Page Numbers: 2055-65

Journal Abbreviation: Exp. Cell Res.

ISSN: 1090-2422

DAY: 5

MONTH: 03

YEAR: 2008

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LANGUAGE: eng

NlmUniqueID: 373226

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Grant and Affiliation Information for LRRK2 regulates synaptic vesicle endocytosis.

AFFILIATION: Department of Life Science, GIST, Buk-gu, Gwangju, South Korea.

Country: United States

AGENCY: United States NIMH

GRANT: MH48866

ACRONYM: MH

MEDLINETA: Exp Cell Res

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