In vivo modulation of polo-like kinases supports a key role for PLK2 in Ser129 α-synuclein phosphorylation in mouse brain

Neuroscience

Volumn 256, Issue , 2014, Pages 72-82

  Bergeron, M ^a   Motter, R ^a   Tanaka, P ^a   Fauss, D ^a   Babcock, M ^a   Chiou, S s ^a   Nelson, S ^a   San Pablo, F ^a   Anderson, J P ^a  

^a ELAN PHARMACEUTICALS   (United States)

Author keywords

BI 2536; Brain; Parkinson's disease; PLK2; Polo like kinase; Synuclein

Indexed keywords

4 (8 CYCLOPENTYL 7 ETHYL 5,6,7,8 TETRAHYDRO 5 METHYL 6 OXO 2 PTERIDINYLAMINO) 3 METHOXY N (1 METHYL 4 PIPERIDINYL)BENZAMIDE; ALPHA SYNUCLEIN; CASEIN KINASE II; G PROTEIN COUPLED RECEPTOR KINASE 5; G PROTEIN COUPLED RECEPTOR KINASE 6; MESSENGER RNA; POLO LIKE KINASE 2; POLO LIKE KINASE 3; SERINE; ENZYME INHIBITOR; G PROTEIN COUPLED RECEPTOR KINASE; G-PROTEIN-COUPLED RECEPTOR KINASE 6; GPRK5 PROTEIN, MOUSE; PLK3 PROTEIN, MOUSE; PROTEIN SERINE THREONINE KINASE; PTERIDINE DERIVATIVE; SERUM-INDUCIBLE KINASE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN; BRAIN LEVEL; CONTROLLED STUDY; ENZYME ACTIVITY; GENE SILENCING; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; ANALYSIS OF VARIANCE; ANIMAL; CHEMISTRY; DEFICIENCY; DRUG EFFECTS; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE EXPRESSION REGULATION; GENETICS; KNOCKOUT MOUSE; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY;

ALPHA-SYNUCLEIN; ANALYSIS OF VARIANCE; ANIMALS; BRAIN; ENZYME INHIBITORS; ENZYME-LINKED IMMUNOSORBENT ASSAY; G-PROTEIN-COUPLED RECEPTOR KINASE 5; G-PROTEIN-COUPLED RECEPTOR KINASES; GENE EXPRESSION REGULATION; MICE; MICE, KNOCKOUT; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; PTERIDINES; RNA, MESSENGER; SERINE;

EID: 84887510168     PISSN: 03064522     EISSN: 18737544     Source Type: Journal    
DOI: 10.1016/j.neuroscience.2013.09.061     Document Type: Article

References (49)

1. Anderson J.P., Walker D.E., Goldstein J.M., de Laat R., Banducci K., Caccavello R.J., Barbour R., Huang J., Kling K., Lee M., Diep L., Keim P.S., Shen X., Chataway T., Schlossmacher M.G., Seubert P., Schenk D., Sinha S., Gai W.P., Chilcote T.J. Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem 2006, 281:29739-29752.
2. Arawaka S., Wada M., Goto S., Karube H., Sakamoto M., Ren C.H., Koyama S., Nagasawa H., Kimura H., Kawanami T., Kurita K., Tajima K., Daimon M., Baba M., Kido T., Saino S., Goto K., Asao H., Kitanaka C., Takashita E., Hongo S., Nakamura T., Kayama T., Suzuki Y., Kobayashi K., Katagiri T., Kurokawa K., Kurimura M., Toyoshima I., Niizato K., Tsuchiya K., Iwatsubo T., Muramatsu M., Matsumine H., Kato T. The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease. J Neurosci 2006, 26:9227-9238.
3. Aubele D.L., Hom R.K., Adler M., Galemmo R.A., Bowers S., Truong A.P., Pan H., Beroza P., Neitz R.J., Yao N., Lin M., Tonn G., Zhang H., Bova M.P., Ren Z., Tam D., Ruslim L., Baker J., Diep L., Fitzgerald K., Hoffman J., Motter R., Fauss D., Tanaka P., Dappen M., Jagodzinski J., Chan W., Konradi A.W., Latimer L., Zhu Y.L., Sham H.L., Anderson J.P., Bergeron M., Artis D.R. Selective and brain-permeable Polo-Like Kinase-2 (Plk-2) inhibitors that reduce α-synuclein phosphorylation in rat brain. ChemMedChem 2013, 8:1295-1313.
4. Bowers S., Truong A.P., Ye M., Aubele D.L., Sealy J.M., Neitz R.J., Hom R.K., Chan W., Dappen M.S., Galemmo R.A., Konradi A.W., Sham H.L., Zhu Y.L., Beroza P., Tonn G., Zhang H., Hoffman J., Motter R., Fauss D., Tanaka P., Bova M.P., Ren Z., Tam D., Ruslim L., Baker J., Pandya D., Diep L., Fitzgerald K., Artis D.R., Anderson J.P., Bergeron M. Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors. Bioorg Med Chem Lett 2013, 23:2743-2749.
5. Braak H., Del Tredici K., Bratzke H., Hamm-Clement J., Sandmann-Keil D., Rüb U. Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease (preclinical and clinical stages). J Neurol 2002, 249(Suppl. 3):III/1-III/5.
6. Braithwaite S.P., Stock J.B., Mouradian M.M. α-Synuclein phosphorylation as a therapeutic target in Parkinson's disease. Rev Neurosci 2012, 23:191-198.
7. Chartier-Harlin M.C., Kachergus J., Roumier C., Mouroux V., Douay X., Lincoln S., Levecque C., Larvor L., Andrieux J., Hulihan M., Waucquier N., Defebvre L., Amouyel P., Farrer M., Destée A. Alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 2004, 364:1167-1169.
8. Chau K.Y., Ching H.L., Schapira A.H., Cooper J.M. Relationship between alpha synuclein phosphorylation, proteasomal inhibition and cell death: relevance to Parkinson's disease pathogenesis. J Neurochem 2009, 110:1005-1013.
9. Chen L., Feany M.B. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci 2005, 8:657-663.
10. de Cárcer G., Manning G., Malumbres M. From Plk1 to Plk5: functional evolution of polo-like kinases. Cell Cycle 2011, 10:2255-2262.
11. Ebrahimi-Fakhari D., Wahlster L., McLean P.J. Protein degradation pathways in Parkinson's disease: curse or blessing. Acta Neuropathol 2012, 124:153-172.
12. Erdtmann-Vourliotis M., Mayer P., Ammon S., Riechert U., Höllt V. Distribution of G-protein-coupled receptor kinase (GRK) isoforms 2, 3, 5 and 6 mRNA in the rat brain. Mol Brain Res 2001, 95:129-137.
13. Fauss D., Motter R., Seto P., Dofiles L., Yu M., Diepp L., Tanaka K., Baker J., Bergeron M. Development of an enzyme-linked immunosorbant assay to measure tyrosine hydroxylase protein in brain tissue from Parkinson's disease models. J Neurosci Methods 2013, 215:245-257.
14. Fitzgerald K., Bergeron M., Willits C., Bowers S., Aubele D.L., Goldbach E., Tonn G., Ness D., Olaharski A. Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei. Toxicol Appl Pharmacol 2013, 269:1-7.
15. Fujiwara H., Hasegawa M., Dohmae N., Kawashima A., Masliah E., Goldberg M.S., Shen J., Takio K., Iwatsubo T. Alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 2002, 4:160-164.
16. Inglis K.J., Chereau D., Brigham E.F., Chiou S.S., Schöbel S., Frigon N.L., Yu M., Caccavello R.J., Nelson S., Motter R., Wright S., Chian D., Santiago P., Soriano F., Ramos C., Powell K., Goldstein J.M., Babcock M., Yednock T., Bard F., Basi G.S., Sham H., Chilcote T.J., McConlogue L., Griswold-Prenner I., Anderson J.P. Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. J Biol Chem 2009, 284:2598-2602.
17. Ishii A., Nonaka T., Taniguchi S., Saito T., Arai T., Mann D., Iwatsubo T., Hisanaga S., Goedert M., Hasegawa M. Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: implication for alpha-synucleinopathies. FEBS Lett 2007, 581:4711-4717.
18. Kauselmann G., Weiler M., Wulff P., Jessberger S., Konietzko U., Scafidi J., Staubli U., Bereiter-Hahn J., Strebhardt K., Kuhl D. The polo-like protein kinases Fnk and Snk associate with a Ca(2+)- and integrin-binding protein and are regulated dynamically with synaptic plasticity. EMBO J 1999, 18:5528-5539.
19. Khandelwal P.J., Dumanis S.B., Feng L.R., Maguire-Zeiss K., Rebeck G., Lashuel H.A., Moussa C.E. Parkinson-related parkin reduces α-Synuclein phosphorylation in a gene transfer model. Mol Cell Neurosci 2012, 49:44-53.
20. Lowery D.M., Lim D., Yaffe M.B. Structure and function of Polo-like kinases. Oncogene 2005, 24:248-259.
21. Ma S., Charron J., Erikson R.L. Role of Plk2 (Snk) in mouse development and cell proliferation. Mol Cell Biol 2003, 23:6936-6943.
22. Machiya Y., Hara S., Arawaka S., Fukushima S., Sato H., Sakamoto M., Koyama S., Kato T. Phosphorylated alpha-synuclein at Ser-129 is targeted to the proteasome pathway in a ubiquitin-independent manner. J Biol Chem 2010, 285:40732-40744.
23. McCormack A.L., Mak S.K., Di Monte D.A. Increased α-synuclein phosphorylation and nitration in the aging primate substantia nigra. Cell Death Dis 2012, 3:e315.
24. McCormack A.L., Mak S.K., Shenasa M., Langston W.J., Forno L.S., Di Monte D.A. Pathologic modifications of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated squirrel monkeys. J Neuropathol Exp Neurol 2008, 67:793-802.
25. Mbefo M.K., Paleologou K.E., Boucharaba A., Oueslati A., Schell H., Fournier M., Olschewski D., Yin G., Zweckstetter M., Masliah E., Kahle P.J., Hirling H., Lashuel H.A. Phosphorylation of synucleins by members of the Polo-like kinase family. J Biol Chem 2010, 285:2807-2822.
26. Mori F., Tanji K., Yoshimoto M., Takahashi H., Wakabayashi K. Immunohistochemical comparison of alpha- and beta-synuclein in adult rat central nervous system. Brain Res 2002, 941:118-126.
27. Okochi M., Walter J., Koyama A., Nakajo S., Baba M., Iwatsubo T., Meijer L., Kahle P.J., Haass C. Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. J Biol Chem 2000, 275:390-397.
28. Oueslati A., Fournier M., Lashuel H.A. Role of post-translational modifications in modulating the structure, function and toxicity of alpha-synuclein: implications for Parkinson's disease pathogenesis and therapies. Prog Brain Res 2010, 183:115-145.
29. Pak D.T., Sheng M. Targeted protein degradation and synapse remodeling by an inducible protein kinase. Science 2003, 302:1368-1373.
30. Paxinos G., Franklin K.B.J. The mouse brain in stereotaxic coordinates 2001, Academic Press. Second ed.
31. 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 2000, 275:26515-26522.
32. Rieker C., Dev K.K., Lehnhoff K., Barbieri S., Ksiazek I., Kauffmann S., Danner S., Schell H., Boden C., Ruegg M.A., Kahle P.J., van der Putten H., Shimshek D.R. Neuropathology in mice expressing mouse alpha-synuclein. PLoS One 2011, 6:e24834.
33. Rozeboom A.M., Pak D.T. Identification and functional characterization of polo-like kinase 2 autoregulatory sites. Neuroscience 2012, 202:147-157.
34. Ryu M.Y., Kim D.W., Arima K., Mouradian M.M., Kim S.U., Lee G. Localization of CKII beta subunits in Lewy bodies of Parkinson's disease. J Neurol Sci 2008, 266:9-12.
35. Saito Y., Kawashima A., Ruberu N.N., Fujiwara H., Koyama S., Sawabe M., Arai T., Nagura H., Yamanouchi H., Hasegawa M., Iwatsubo T., Murayama S. Accumulation of phosphorylated alpha-synuclein in aging human brain. J Neuropathol Exp Neurol 2003, 62:644-654.
36. Sato H., Kato T., Arawaka S. The role of Ser129 phosphorylation of α-synuclein in neurodegeneration of Parkinson's disease: a review of in vivo models. Rev Neurosci 2013, 9:1-9.
37. Schell H., Hasegawa T., Neumann M., Kahle P.J. Nuclear and neuritic distribution of serine-129 phosphorylated alpha-synuclein in transgenic mice. Neuroscience 2009, 160:796-804.
38. Schoebel S., Yu M., Nelson S., Chiou S.-S., Chereau D., Cutcliffe C., Mehra N., Johnston J.A., Anderson J.P. Proteosomal inhibition increases phospho-synuclein levels. Soc Neurosci Abstr 2009, 35(629):20.
39. Seeburg D.P., Pak D., Sheng M. Polo-like kinases in the nervous system. Oncogene 2005, 24:292-298.
40. Singleton A.B., Farrer M., Johnson J., Singleton A., Hague S., Kachergus J., Hulihan M., Peuralinna T., Dutra A., Nussbaum R., Lincoln S., Crawley A., Hanson M., Maraganore D., Adler C., Cookson M.R., Muenter M., Baptista M., Miller D., Blancato J., Hardy J., Gwinn-Hardy K. Alpha-Synuclein locus triplication causes Parkinson's disease. Science 2003, 302:841.
41. Steegmaier M., Hoffmann M., Baum A., Lénárt P., Petronczki M., Krssák M., Gürtler U., Garin-Chesa P., Lieb S., Quant J., Grauert M., Adolf G.R., Kraut N., Peters J.M., Rettig W.J. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Curr Biol 2007, 17:316-322.
42. van de Weerdt B.C., Littler D.R., Klompmaker R., Huseinovic A., Fish A., Perrakis A., Medema R.H. Polo-box domains confer target specificity to the Polo-like kinase family. Biochim Biophys Acta 2008, 1783:1015-1022.
43. Visanji N.P., Wislet-Gendebien S., Oschipok L.W., Zhang G., Aubert I., Fraser P.E., Tandon A. Effect of Ser-129 phosphorylation on interaction of α-synuclein with synaptic and cellular membranes. J Biol Chem 2011, 286:35863-35873.
44. Vivacqua G., Casini A., Vaccaro R., Fornai F., Yu S., D'Este L. Different sub-cellular localization of alpha-synuclein in the C57BL/6J mouse's central nervous system by two novel monoclonal antibodies. J Chem Neuroanat 2011, 41:97-110.
45. Wakamatsu M., Ishii A., Ukai Y., Sakagami J., Iwata S., Ono M., Matsumoto K., Nakamura A., Tada N., Kobayashi K., Iwatsubo T., Yoshimoto M. Accumulation of phosphorylated alpha-synuclein in dopaminergic neurons of transgenic mice that express human alpha-synuclein. J Neurosci Res 2007, 85:1819-1825.
46. Waxman E.A., Giasson B.I. Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synuclein. J Neuropathol Exp Neurol 2008, 67:402-416.
47. Yu S., Li X., Liu G., Han J., Zhang C., Li Y., Xu S., Liu C., Gao Y., Yang H., Uéda K., Chan P. Extensive nuclear localization of alpha-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. Neuroscience 2007, 145:539-555.
48. Zarranz J.J., Alegre J., Gómez-Esteban J.C., Lezcano E., Ros R., Ampuero I., Vidal L., Hoenicka J., Rodriguez O., Atarés B., Llorens V., Gomez Tortosa E., del Ser T., Muñoz D.G., de Yebenes J.G. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 2004, 55:164-173.
49. Zhou J., Broe M., Huang Y., Anderson J.P., Gai W.P., Milward E.A., Porritt M., Howells D., Hughes A.J., Wang X., Halliday G.M. Changes in the solubility and phosphorylation of α-synuclein over the course of Parkinson's disease. Acta Neuropathol 2011, 121:695-704.