LK6/Mnk2a is a new kinase of alpha synuclein phosphorylation mediating neurodegeneration

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Zhang, Shiqing ^a   Xie, Jiang ^a   Xia, Ying ^a   Yu, Shu ^a   Gu, Zhili ^a   Feng, Ruili ^a   Luo, Guanghong ^a   Wang, Dong ^a   Wang, Kai ^a   Jiang, Meng ^a   Cheng, Xiao ^a   Huang, Hai ^a   Zhang, Wu ^a   Wen, Tieqiao ^a  

^a SHANGHAI UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; DROSOPHILA PROTEIN; LK6 PROTEIN, DROSOPHILA; MITOGEN ACTIVATED PROTEIN KINASE KINASE; PHOSPHOTRANSFERASE;

ANIMAL; DISEASE MODEL; DOPAMINERGIC NERVE CELL; DROSOPHILA; FEMALE; MALE; METABOLISM; NERVE DEGENERATION; PARKINSON DISEASE; PHOSPHORYLATION; PHYSIOLOGY; SIGNAL TRANSDUCTION; SUBSTANTIA NIGRA;

ALPHA-SYNUCLEIN; ANIMALS; DISEASE MODELS, ANIMAL; DOPAMINERGIC NEURONS; DROSOPHILA; DROSOPHILA PROTEINS; FEMALE; MALE; MAP KINASE SIGNALING SYSTEM; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; NERVE DEGENERATION; PARKINSON DISEASE; PHOSPHORYLATION; PHOSPHOTRANSFERASES; SIGNAL TRANSDUCTION; SUBSTANTIA NIGRA;

EID: 84938124721     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep12564     Document Type: Article

References (56)

1. Karuppagounder, S. S. et al. The c-Abl inhibitor, nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson's disease. Sci Rep 4, 4874 (2014).
2. Jiang, P. et al. Adenosine monophosphate-activated protein kinase overactivation leads to accumulation of alpha-synuclein oligomers and decrease of neurites. Neurobiol Aging 34, 1504-1515 (2013).
3. Wolters, E. Variability in the clinical expression of Parkinson's disease. J Neurol Sci 266, 197-203 (2008).
4. Polymeropoulos, M. H. et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047 (1997).
5. Sandal, M. et al. Conformational equilibria in monomeric alpha-synuclein at the single-molecule level. PLoS Biol 6, e6 (2008).
6. Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-608 (1998).
7. von Coelln, R., Dawson, V. L. & Dawson, T. M. Parkin-associated Parkinson's disease. Cell Tissue Res 318, 175-184 (2004).
8. da Costa, C. A. DJ-1: a newcomer in Parkinson's disease pathology. Curr Mol Med 7, 650-657 (2007).
9. Bonifati, V. et al. DJ-1(PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol Sci 24, 159-160 (2003).
10. Dawson, T. M. & Dawson, V. L. Molecular pathways of neurodegeneration in Parkinson's disease. Science 302, 819-822 (2003).
11. Keeney, P. M., Xie, J., Capaldi, R. A. & Bennett, J. P., Jr. Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci 26, 5256-5264 (2006).
12. Sohmiya, M. et al. Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson's disease. J Neurol Sci 223, 161-166 (2004).
13. Goedert, M. Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2, 492-501 (2001).
14. Bae, E. J. et al. Glucocerebrosidase depletion enhances cell-to-cell transmission of alpha-synuclein. Nat Commun 5, 4755 (2014).
15. Lee, V. M. & Trojanowski, J. Q. Mechanisms of Parkinson's disease linked to pathological alpha-synuclein: new targets for drug discovery. Neuron 52, 33-38 (2006).
16. Olanow, C. W. & McNaught, K. S. Ubiquitin-proteasome system and Parkinson's disease. Mov Disord 21, 1806-1823 (2006).
17. Li, J., Uversky, V. N. & Fink, A. L. Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein. Biochemistry 40, 11604-11613 (2001).
18. Kruger, R. et al. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 18, 106-108 (1998).
19. Dev, K. K., Hofele, K., Barbieri, S., Buchman, V. L. & van der Putten, H. Part II: alpha-synuclein and its molecular pathophysiological role in neurodegenerative disease. Neuropharmacology 45, 14-44 (2003).
20. Arawaka, S. et al. The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease. J Neurosci 26, 9227-9238 (2006).
21. Smith, W. W. et al. Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells. J Neurosci 25, 5544-5552 (2005).
22. Basso, E. et al. PLK2 Modulates alpha-Synuclein Aggregation in Yeast and Mammalian Cells. Mol Neurobiol 48, 854-862 (2013).
23. Okochi, M. et al. Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. J Biol Chem 275, 390-397 (2000).
24. Ishii, A. et al. Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies. FEBS Lett 581, 4711-4717 (2007).
25. Dzamko, N., Zhou, J., Huang, Y. & Halliday, G. M. Parkinson's disease-implicated kinases in the brain; insights into disease pathogenesis. Frontiers in molecular neuroscience 7, 57 (2014).
26. Pronin, A. N., Morris, A. J., Surguchov, A. & Benovic, J. L. Synucleins are a novel class of substrates for G protein-coupled receptor kinases. J Biol Chem 275, 26515-26522 (2000).
27. Inglis, K. J. et al. Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. J Biol Chem 284, 2598-2602 (2009).
28. Qing, H., Wong, W., McGeer, E. G. & McGeer, P. L. Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications. Biochem Biophys Res Commun 387, 149-152 (2009).
29. Ardley, H. C., Scott, G. B., Rose, S. A., Tan, N. G. & Robinson, P. A. UCH-L1 aggresome formation in response to proteasome impairment indicates a role in inclusion formation in Parkinson's disease. J Neurochem 90, 379-391 (2004).
30. Liang, J. et al. Novel suppressors of alpha-synuclein toxicity identified using yeast. Hum Mol Genet 17, 3784-3795 (2008).
31. Yan, X. et al. Proteomic profiling of the insoluble pellets of the transected rat spinal cord. J Neurotrauma 26, 179-193 (2009).
32. Chung, S. J. et al. Common variants in PARK loci and related genes and Parkinson's disease. Mov Disord 26, 280-288 (2011).
33. Kay, D. M. et al. A comprehensive analysis of deletions, multiplications, and copy number variations in PARK2. Neurology 75, 1189-1194 (2010).
34. Bjorklund, M. et al. Identification of pathways regulating cell size and cell-cycle progression by RNAi. Nature 439, 1009-1013 (2006).
35. Powell, D. W. et al. Proteomic identification of 14-3-3zeta as a mitogen-activated protein kinase-activated protein kinase 2 substrate: role in dimer formation and ligand binding. Molecular and cellular biology 23, 5376-5387 (2003).
36. Parra-Palau, J. L., Scheper, G. C., Harper, D. E. & Proud, C. G. The Drosophila protein kinase LK6 is regulated by ERK and phosphorylates the eukaryotic initiation factor eIF4E in vivo. The Biochemical journal 385, 695-702 (2005).
37. Olsen, B. B., Svenstrup, T. H. & Guerra, B. Downregulation of protein kinase CK2 induces autophagic cell death through modulation of the mTOR and MAPK signaling pathways in human glioblastoma cells. International journal of oncology 41, 1967-1976 (2012).
38. Chin, L. S., Olzmann, J. A. & Li, L. Parkin-mediated ubiquitin signalling in aggresome formation and autophagy. Biochem Soc Trans 38, 144-149 (2010).
39. Ziviani, E. & Whitworth, A. J. How could Parkin-mediated ubiquitination of mitofusin promote mitophagy? Autophagy 6, 660-662 (2010).
40. Arquier, N., Bourouis, M., Colombani, J. & Leopold, P. Drosophila Lk6 kinase controls phosphorylation of eukaryotic translation initiation factor 4E and promotes normal growth and development. Curr Biol 15, 19-23 (2005).
41. Wang, J., Lou, H., Pedersen, C. J., Smith, A. D. & Perez, R. G. 14-3-3zeta contributes to tyrosine hydroxylase activity in MN9D cells: localization of dopamine regulatory proteins to mitochondria. J Biol Chem 284, 14011-14019 (2009).
42. Chen, L. & Feany, M. B. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci 8, 657-663 (2005).
43. Spillantini, M. G. et al. Alpha-synuclein in Lewy bodies. Nature 388, 839-840 (1997).
44. Sakamoto, M. et al. Contribution of endogenous G-protein-coupled receptor kinases to Ser129 phosphorylation of alphasynuclein in HEK293 cells. Biochem Biophys Res Commun 384, 378-382 (2009).
45. Scheper, G. C. et al. The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization. Mol Cell Biol 23, 5692-5705 (2003).
46. Scheper, G. C., Morrice, N. A., Kleijn, M. & Proud, C. G. The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells. Mol Cell Biol 21, 743-754 (2001).
47. Iwata, A., Maruyama, M., Kanazawa, I. & Nukina, N. alpha-Synuclein affects the MAPK pathway and accelerates cell death. The Journal of biological chemistry 276, 45320-45329 (2001).
48. Coleman, J. A. & Molday, R. S. Critical role of the beta-subunit CDC50A in the stable expression, assembly, subcellular localization, and lipid transport activity of the P4-ATPase ATP8A2. The Journal of biological chemistry 286, 17205-17216 (2011).
49. Emery, P. RNA extraction from Drosophila heads. Methods Mol Biol 362, 305-307 (2007).
50. Zhang, Y. Q. et al. Protein expression profiling of the drosophila fragile X mutant brain reveals up-regulation of monoamine synthesis. Mol Cell Proteomics 4, 278-290 (2005).
51. Schaefer, U., Schmeier, S. & Bajic, V. B. TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins. Nucleic Acids Res 39, D106-110 (2011).
52. Xenarios, I. et al. DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions. Nucleic Acids Res 30, 303-305 (2002).
53. Bandyopadhyay, S., Sharan, R. & Ideker, T. Systematic identification of functional orthologs based on protein network comparison. Genome Res 16, 428-435 (2006).
54. Mishra, G. R. et al. Human protein reference database-2006 update. Nucleic Acids Res 34, D411-414 (2006).
55. Alessi, D. R., Cuenda, A., Cohen, P., Dudley, D. T. & Saltiel, A. R. PD 098059 is a specific inhibitor of the activation of mitogenactivated protein kinase kinase in vitro and in vivo. J Biol Chem 270, 27489-27494 (1995).
56. Nielsen, M. et al. Cause-specific mortality among spouses of Parkinson disease patients. Epidemiology 25, 225-232 (2014).