Identification of protein phosphatase 2A as an interacting protein of leucine-rich repeat kinase 2
| Autor: | Panagiotis S. Athanasopoulos, Christian Herrmann, Sebastian Neumann, Miriam Kutsch, Wright Jacob, Zoë Bichler, Dirk Wolters, Rolf Heumann, Eng-King Tan |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Protein subunit Clinical Biochemistry Leucine-rich repeat Biology Selenic Acid Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Biochemistry 03 medical and health sciences Downregulation and upregulation Catalytic Domain medicine Humans Protein Phosphatase 2 Molecular Biology G alpha subunit Cell Nucleus Neurons Cell Death Kinase Neurodegeneration Protein phosphatase 2 medicine.disease LRRK2 Molecular biology nervous system diseases 030104 developmental biology Gene Knockdown Techniques HeLa Cells Protein Binding |
| Zdroj: | Biological chemistry. 397(6) |
| ISSN: | 1437-4315 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|