Please use this identifier to cite or link to this item: https://doi.org/10.1515/hsz-2015-0189
Title: Identification of protein phosphatase 2A as an interacting protein of leucine-rich repeat kinase 2
Authors: Athanasopoulos P.S.
Jacob W.
Neumann S.
Kutsch M.
Wolters D.
Tan E.K. 
Bichler Z. 
Herrmann C.
Heumann R.
Keywords: G2019S
neurodegeneration
neuroprotection
R1441C
ROC
sodium selenate
Issue Date: 2016
Publisher: Walter de Gruyter GmbH
Citation: Athanasopoulos P.S., Jacob W., Neumann S., Kutsch M., Wolters D., Tan E.K., Bichler Z., Herrmann C., Heumann R. (2016). Identification of protein phosphatase 2A as an interacting protein of leucine-rich repeat kinase 2. Biological Chemistry 397 (6) : 541-554. ScholarBank@NUS Repository. https://doi.org/10.1515/hsz-2015-0189
Abstract: Mutations in the gene coding for the multi-domain protein leucine-rich repeat kinase 2 (LRRK2) are the leading cause of genetically inherited Parkinson's disease (PD). Two of the common found mutations are the R1441C and G2019S. In this study we identified protein phosphatase 2A (PP2A) as an interacting partner of LRRK2. We were able to demonstrate that the Ras of complex protein (ROC) domain is sufficient to interact with the three subunits of PP2A in human neuroblastoma SH-SY5Y cells and in HeLa cells. The alpha subunit of PP2A is interacting with LRRK2 in the perinuclear region of HeLa cells. Silencing the catalytic subunit of PP2A by shRNA aggravated cellular degeneration induced by the pathogenic R1441C-LRRK2 mutant expressed in neuroblastoma SH-SY5Y cells. A similar enhancement of apoptotic nuclei was observed by downregulation of the catalytic subunit of PP2A in cultured cortical cells derived from neurons overexpressing the pathogenic mutant G2019S-LRRK2. Conversely, pharmacological activation of PP2A by sodium selenate showed a partial neuroprotection from R1441C-LRRK2-induced cellular degeneration. All these data suggest that PP2A is a new interacting partner of LRRK2 and reveal the importance of PP2A as a potential therapeutic target in PD. � 2016 by De Gruyter.
Source Title: Biological Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/149008
ISSN: 14316730
DOI: 10.1515/hsz-2015-0189
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