Arsenite stress down-regulates phosphorylation and 14-3-3 binding of leucine-rich repeat kinase 2 (LRRK2), promoting self-association and cellular redistribution

Journal of Biological Chemistry

Volumn 289, Issue 31, 2014, Pages 21386-21400

  Mamais, Adamantios ^a,b,c   Chia, Ruth ^c,d   Beilina, Alexandra ^c   Hauser, David N ^c,e   Hall, Christine ^b   Lewis, Patrick A ^b,f   Cookson, Mark R ^c   Bandopadhyay, Rina ^a,b  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c NATIONAL INSTITUTE ON AGING   (United States)

^d GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^e BROWN UNIVERSITY   (United States)

^f UNIVERSITY OF READING   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; GENE ENCODING; PHOSPHATASES; PHOSPHORYLATION;

DEPHOSPHORYLATIONS; LEUCINE-RICH REPEATS; PARKINSON DISEASE; PATHOGENIC MUTATION; PHARMACOLOGICAL INHIBITION; PROTEIN PHOSPHATASE-1; SELF-ASSOCIATIONS; SIGNALING EVENTS;

ASSOCIATION REACTIONS;

ARSENIC TRIOXIDE; GUANOSINE TRIPHOSPHATE; HYDROGEN PEROXIDE; LEUCINE RICH REPEAT KINASE 2; PHOSPHATASE; PROTEIN 14 3 3; PROTEIN PHOSPHATASE 1ALPHA; UNCLASSIFIED DRUG; ARSENOUS ACID DERIVATIVE; LRRK2 PROTEIN, HUMAN; PROTEIN BINDING; PROTEIN SERINE THREONINE KINASE;

ARTICLE; CELLULAR DISTRIBUTION; CENTROSOME; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INHIBITION; GEL PERMEATION CHROMATOGRAPHY; HEK293 CELL LINE; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; IN VITRO STUDY; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; WESTERN BLOTTING; WILD TYPE; DRUG EFFECTS; METABOLISM; PHOSPHORYLATION; PHYSIOLOGICAL STRESS;

14-3-3 PROTEINS; ARSENITES; DOWN-REGULATION; HEK293 CELLS; HUMANS; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN-SERINE-THREONINE KINASES; STRESS, PHYSIOLOGICAL;

EID: 84905398360     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.528463     Document Type: Article

References (66)

1. Halliday, G., Lees, A., and Stern, M. (2011) Milestones in Parkinson's disease: clinical and pathologic features. Mov. Disord. 26, 1015-1021
2. Cookson, M. R., and Bandmann, O. (2010) Parkinson's disease: insights from pathways. Hum. Mol. Genet. 19, R21-R27
3. Hardy, J. (2010) Genetic analysis of pathways to Parkinson disease. Neuron 68, 201-206
4. Paisán-Ruíz, C., Jain, S., Evans, E. W., Gilks, W. P., Simón, J., van der Brug, M., López de Munain, A., Aparicio, S., Gil, A. M., Khan, N., Johnson, J., Martinez, J. R., Nicholl, D., Carrera, I. M., Pena, A. S., de Silva, R., Lees, A., Martí-Massó, J. F., Pérez-Tur, J., Wood, N. W., and Singleton, A. B. (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44, 595-600
5. Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., Kachergus, J., Hulihan, M., Uitti, R. J., Calne, D. B., Stoessl, A. J., Pfeiffer, R. F., Patenge, N., Carbajal, I. C., Vieregge, P., Asmus, F., Müller-Myhsok, B., Dickson, D. W., Meitinger, T., Strom, T. M., Wszolek, Z. K., and Gasser, T. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601-607 (Pubitemid 39531225)
6. Dächsel, J. C., and Farrer, M. J. (2010) LRRK2 and Parkinson disease. Arch. Neurol. 67, 542-547
7. Greggio, E., Zambrano, I., Kaganovich, A., Beilina, A., Taymans, J.-M., Daniëls, V., Lewis, P., Jain, S., Ding, J., Syed, A., Thomas, K. J., Baekelandt, V., and Cookson, M. R. (2008) The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation. J. Biol. Chem. 283, 16906-16914
8. Daniëls, V., Vancraenenbroeck, R., Law, B. M. H., Greggio, E., Lobbestael, E., Gao, F., De Maeyer, M., Cookson, M. R., Harvey, K., Baekelandt, V., and Taymans, J.-M. (2011) Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant. J. Neurochem. 116, 304-315
9. Mata, I. F., Wedemeyer, W. J., Farrer, M. J., Taylor, J. P., and Gallo, K. A. (2006) LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci. 29, 286-293
10. Greggio, E., Jain, S., Kingsbury, A., Bandopadhyay, R., Lewis, P., Kaganovich, A., van der Brug, M. P., Beilina, A., Blackinton, J., Thomas, K. J., Ahmad, R., Miller, D. W., Kesavapany, S., Singleton, A., Lees, A., Harvey, R. J., Harvey, K., and Cookson, M. R. (2006) Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol. Dis. 23, 329-341 (Pubitemid 44097032)
11. West, A. B., Moore, D. J., Choi, C., Andrabi, S. A., Li, X., Dikeman, D., Biskup, S., Zhang, Z., Lim, K.-L., Dawson, V. L., and Dawson, T. M. (2007) Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-FIGURE binding and kinase activities to neuronal toxicity. Hum. Mol. Genet. 16, 223-232 (Pubitemid 46179004)
12. Dusonchet, J., Kochubey, O., Stafa, K., Young, S. M., Jr., Zufferey, R., Moore, D. J., Schneider, B. L., and Aebischer, P. (2011) A rat model of progressive nigral neurodegeneration induced by the Parkinson's disease-associated G2019S mutation in LRRK2. J. Neurosci. 31, 907-912
13. Dzamko, N., Deak, M., Hentati, F., Reith, A. D., Prescott, A. R., Alessi, D. R., and Nichols, R. J. (2010) Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser910/Ser935, disruption of 14-3-3 binding and altered cytoplasmic localization. Biochem. J. 430, 405-413
14. Nichols, R. J., Dzamko, N., Morrice, N. A., Campbell, D. G., Deak, M., Ordureau, A., Macartney, T., Tong, Y., Shen, J., Prescott, A. R., and Alessi, D. R. (2010) 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization. Biochem. J. 430, 393-404
15. Deng, X., Dzamko, N., Prescott, A., Davies, P., Liu, Q., Yang, Q., Lee, J.-D., Patricelli, M. P., Nomanbhoy, T. K., Alessi, D. R., and Gray, N. S. (2011) Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2. Nat. Chem. Biol. 7, 203-205
16. Rudenko, I. N., Kaganovich, A., Hauser, D. N., Beylina, A., Chia, R., Ding, J., Maric, D., Jaffe, H., and Cookson, M. R. (2012) The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's disease is a partial loss-of-function mutation. Biochem. J. 446, 99-111
17. Dzamko, N., Inesta-Vaquera, F., Zhang, J., Xie, C., Cai, H., Arthur, S., Tan, L., Choi, H., Gray, N., Cohen, P., Pedrioli, P., Clark, K., and Alessi, D. R. (2012) The IκB kinase family phosphorylates the Parkinson's disease kinase LRRK2 at Ser935 and Ser910 during Toll-like receptor signaling. PLoS One 7, e39132
18. Lobbestael, E., Zhao, J., Rudenko, I. N., Beylina, A., Gao, F., Wetter, J., Beullens, M., Bollen, M., Cookson, M. R., Baekelandt, V., Nichols, R. J., and Taymans, J.-M. (2013) Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle. Biochem. J. 456, 119-128
19. Gandhi, S., and Abramov, A. Y. (2012) Mechanism of oxidative stress in neurodegeneration. Oxid. Med. Cell Longev. 2012, 428010
20. Korecka, J. A., Eggers, R., Swaab, D. F., Bossers, K., and Verhaagen, J. (2013) Modeling early Parkinson's disease pathology with chronic low dose MPTP treatment. Restor. Neurol. Neurosci. 31, 155-167
21. Burns, R. S., Chiueh, C. C., Markey, S. P., Ebert, M. H., Jacobowitz, D. M., and Kopin, I. J. (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc. Natl. Acad. Sci. U.S.A. 80, 4546-4550 (Pubitemid 13077876)
22. Pan-Montojo, F., Anichtchik, O., Dening, Y., Knels, L., Pursche, S., Jung, R., Jackson, S., Gille, G., Spillantini, M. G., Reichmann, H., and Funk, R. H. W. (2010) Progression of Parkinson's disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One 5, e8762
23. Betarbet, R., Sherer, T. B., MacKenzie, G., Garcia-Osuna, M., Panov, A. V., and Greenamyre, J. T. (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci. 3, 1301-1306
24. Hsu, C. H., Chan, D., Greggio, E., Saha, S., Guillily, M. D., Ferree, A., Raghavan, K., Shen, G. C., Segal, L., Ryu, H., Cookson, M. R., and Wolozin, B. (2010) MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2. J. Neurochem. 112, 1593-1604
25. Papkovskaia, T. D., Chau, K.-Y., Inesta-Vaquera, F., Papkovsky, D. B., Healy, D. G., Nishio, K., Staddon, J., Duchen, M. R., Hardy, J., Schapira, A. H. V., and Cooper, J. M. (2012) G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. Hum. Mol. Genet. 21, 4201-4213
26. Mortiboys, H., Johansen, K. K., Aasly, J. O., and Bandmann, O. (2010) Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2. Neurology 75, 2017-2020
27. Civiero, L., Vancraenenbroeck, R., Belluzzi, E., Beilina, A., Lobbestael, E., Reyniers, L., Gao, F., Micetic, I., De Maeyer, M., Bubacco, L., Baekelandt, V., Cookson, M. R., Greggio, E., and Taymans, J.-M. (2012) Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers. PLoS One 7, e43472
28. Greggio, E., Lewis, P. A., van der Brug, M. P., Ahmad, R., Kaganovich, A., Ding, J., Beilina, A., Baker, A. K., and Cookson, M. R. (2007) Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1. J. Neurochem. 102, 93-102 (Pubitemid 46906263)
29. Taymans, J.-M., Vancraenenbroeck, R., Ollikainen, P., Beilina, A., Lobbestael, E., De Maeyer, M., Baekelandt, V., and Cookson, M. R. (2011) LRRK2 kinase activity is dependent on LRRK2 GTP binding capacity but independent of LRRK2 GTP binding. PLoS One 6, e23207
30. Nichols, R. J., Dzamko, N., Hutti, J. E., Cantley, L. C., Deak, M., Moran, J., Bamborough, P., Reith, A. D., and Alessi, D. R. (2009) Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease. Biochem. J. 424, 47-60
31. Jaleel, M., Nichols, R. J., Deak, M., Campbell, D. G., Gillardon, F., Knebel, A., and Alessi, D. R. (2007) LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity. Biochem. J. 405, 307-317 (Pubitemid 47075166)
32. Pungaliya, P. P., Bai, Y., Lipinski, K., Anand, V. S., Sen, S., Brown, E. L., Bates, B., Reinhart, P. H., West, A. B., Hirst, W. D., and Braithwaite, S. P. (2010) Identification and characterization of a leucine-rich repeat kinase 2 (LRRK2) consensus phosphorylation motif. PLoS One 5, e13672
33. Sen, S., Webber, P. J., and West, A. B. (2009) Dependence of leucine-rich repeat kinase 2 (LRRK2) kinase activity on dimerization. J. Biol. Chem. 284, 36346-36356
34. Ito, G., and Iwatsubo, T. (2012) Re-examination of the dimerization state of leucine-rich repeat kinase 2: predominance of the monomeric form. Biochem. J. 441, 987-994
35. James, N. G., Digman, M. A., Gratton, E., Barylko, B., Ding, X., Albanesi, J. P., Goldberg, M. S., and Jameson, D. M. (2012) Number and brightness analysis of LRRK2 oligomerization in live cells. Biophys. J. 102, L41-L43
36. Gotthardt, K., Weyand, M., Kortholt, A., Van Haastert, P. J. M., and Wittinghofer, A. (2008) Structure of the Roc-COR domain tandem of C. tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase. EMBO J. 27, 2239-2249
37. Deng, J., Lewis, P. A., Greggio, E., Sluch, E., Beilina, A., and Cookson, M. R. (2008) Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. Proc. Natl. Acad. Sci. U.S.A. 105, 1499-1504 (Pubitemid 351346543)
38. Biosa, A., Trancikova, A., Civiero, L., Glauser, L., Bubacco, L., Greggio, E., and Moore, D. J. (2013) GTPase activity regulates kinase activity and cellular phenotypes of Parkinson's disease-associated LRRK2. Hum. Mol. Genet. 22, 1140-1156
39. Gasper, R., Meyer, S., Gotthardt, K., Sirajuddin, M., and Wittinghofer, A. (2009) It takes two to tango: regulation of G proteins by dimerization. Nat. Rev. Mol. Cell Biol. 10, 423-429
40. Biskup, S., Moore, D. J., Celsi, F., Higashi, S., West, A. B., Andrabi, S. A., Kurkinen, K., Yu, S.-W., Savitt, J. M., Waldvogel, H. J., Faull, R. L. M., Emson, P. C., Torp, R., Ottersen, O. P., Dawson, T. M., and Dawson, V. L. (2006) Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann. Neurol. 60, 557-569 (Pubitemid 44871798)
41. Berger, Z., Smith, K. A., and Lavoie, M. J. (2010) Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation. Biochemistry 49, 5511-5523
42. Fabunmi, R. P., Wigley, W. C., Thomas, P. J., and DeMartino, G. N. (2000) Activity and regulation of the centrosome-associated proteasome. J. Biol. Chem. 275, 409-413 (Pubitemid 30038999)
43. Wigley, W. C., Fabunmi, R. P., Lee, M. G., Marino, C. R., Muallem, S., DeMartino, G. N., and Thomas, P. J. (1999) Dynamic association of proteasomal machinery with the centrosome. J. Cell Biol. 145, 481-490 (Pubitemid 29215713)
44. Ko, H. S., Bailey, R., Smith, W. W., Liu, Z., Shin, J.-H., Lee, Y.-I., Zhang, Y.-J., Jiang, H., Ross, C. A., Moore, D. J., Patterson, C., Petrucelli, L., Dawson, T. M., and Dawson, V. L. (2009) CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. Proc. Natl. Acad. Sci. U.S.A. 106, 2897-2902
45. Orenstein, S. J., Kuo, S.-H., Tasset, I., Arias, E., Koga, H., Fernandez-Carasa, I., Cortes, E., Honig, L. S., Dauer, W., Consiglio, A., Raya, A., Sulzer, D., and Cuervo, A. M. (2013) Interplay of LRRK2 with chaperone-mediated autophagy. Nat. Neurosci. 16, 394-406
46. Kelly, S. M., Vanslyke, J. K., and Musil, L. S. (2007) Regulation of ubiquitin-proteasome system mediated degradation by cytosolic stress. Mol. Biol. Cell 18, 4279-4291 (Pubitemid 350060158)
47. Bond, U., Agell, N., Haas, A. L., Redman, K., and Schlesinger, M. J. (1988) Ubiquitin in stressed chicken embryo fibroblasts. J. Biol. Chem. 263, 2384-2388 (Pubitemid 18060301)
48. Gandhi, P. N., Wang, X., Zhu, X., Chen, S. G., and Wilson-Delfosse, A. L. (2008) The Roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubules. J. Neurosci. Res. 86, 1711-1720 (Pubitemid 351859422)
49. Caesar, M., Zach, S., Carlson, C. B., Brockmann, K., Gasser, T., and Gillardon, F. (2013) Leucine-rich repeat kinase 2 functionally interacts with microtubules and kinase-dependently modulates cell migration. Neurobiol. Dis. 54, 280-288
50. Kamikawaji, S., Ito, G., and Iwatsubo, T. (2009) Identification of the autophosphorylation sites of LRRK2. Biochemistry 48, 10963-10975
51. Greggio, E., Taymans, J.-M., Zhen, E. Y., Ryder, J., Vancraenenbroeck, R., Beilina, A., Sun, P., Deng, J., Jaffe, H., Baekelandt, V., Merchant, K., and Cookson, M. R. (2009) The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites. Biochem. Biophys. Res. Commun. 389, 449-454
52. Webber, P. J., Smith, A. D., Sen, S., Renfrow, M. B., Mobley, J. A., and West, A. B. (2011) Autophosphorylation in the leucine-rich repeat kinase 2 (LRRK2) GTPase domain modifies kinase and GTP-binding activities. J. Mol. Biol. 412, 94-110
53. Sheng, Z., Zhang, S., Bustos, D., Kleinheinz, T., Le Pichon, C. E., Dominguez, S. L., Solanoy, H. O., Drummond, J., Zhang, X., Ding, X., Cai, F., Song, Q., Li, X., Yue, Z., van der Brug, M. P., Burdick, D. J., Gunzner-Toste, J., Chen, H., Liu, X., Estrada, A. A., Sweeney, Z. K., Scearce-Levie, K., Moffat, J. G., Kirkpatrick, D. S., and Zhu, H. (2012) Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations. Sci. Transl. Med. 4, 164ra161
54. Li, X., Moore, D. J., Xiong, Y., Dawson, T. M., and Dawson, V. L. (2010) Reevaluation of phosphorylation sites in the Parkinson disease-associated leucine-rich repeat kinase 2. J. Biol. Chem. 285, 29569-29576
55. Kapahi, P., Takahashi, T., Natoli, G., Adams, S. R., Chen, Y., Tsien, R. Y., and Karin, M. (2000) Inhibition of NF-κB activation by arsenite through reaction with a critical cysteine in the activation loop of IκB kinase. J. Biol. Chem. 275, 36062-36066
56. Fu, H., Subramanian, R. R., and Masters, S. C. (2000) 14-3-3 proteins: structure, function, and regulation. Annu. Rev. Pharmacol. Toxicol. 40, 617-647 (Pubitemid 30340695)
57. Riou, P., Kjær, S., Garg, R., Purkiss, A., George, R., Cain, R. J., Bineva, G., Reymond, N., McColl, B., Thompson, A. J., O'Reilly, N., McDonald, N. Q., Parker, P. J., and Ridley, A. J. (2013) 14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins. Cell 153, 640-653
58. Jorgensen, N. D., Peng, Y., Ho, C. C.-Y., Rideout, H. J., Petrey, D., Liu, P., and Dauer, W. T. (2009) The WD40 domain is required for LRRK2 neurotoxicity. PLoS One 4, e8463
59. Kenney, L. J., and Kaplan, J. H. (1988) Arsenate substitutes for phosphate in the human red cell sodium pump and anion exchanger. J. Biol. Chem. 263, 7954-7960
60. Roussel, R. R., and Barchowsky, A. (2000) Arsenic inhibits NF-κB-mediated gene transcription by blocking IκBkinase activity and IκBα phosphorylation and degradation. Arch. Biochem. Biophys. 377, 204-212 (Pubitemid 30257306)
61. Waxman, E. A., Covy, J. P., Bukh, I., Li, X., Dawson, T. M., and Giasson, B. I. (2009) Leucine-rich repeat kinase 2 expression leads to aggresome formation that is not associated with α-synuclein inclusions. J. Neuropathol. Exp. Neurol. 68, 785-796
62. Johnston, J. A., Ward, C. L., and Kopito, R. R. (1998) Aggresomes: a cellular response to misfolded proteins. J. Cell Biol. 143, 1883-1898 (Pubitemid 29022611)
63. Samikkannu, T., Chen, C.-H., Yih, L.-H., Wang, A. S. S., Lin, S.-Y., Chen, T.-C., and Jan, K.-Y. (2003) Reactive oxygen species are involved in arsenic trioxide inhibition of pyruvate dehydrogenase activity. Chem. Res. Toxicol. 16, 409-414 (Pubitemid 36373706)
64. Jung, D. K., Bae, G.-U., Kim, Y. K., Han, S.-H., Choi, W. S., Kang, H., Seo, D. W., Lee, H. Y., Cho, E.-J., Lee, H.-W., and Han, J.-W. (2003) Hydrogen peroxide mediates arsenite activation of p70(s6k) and extracellular signal-regulated kinase. Exp. Cell Res. 290, 144-154 (Pubitemid 37153258)
65. Yuan, S. S., Hou, M. F., Chang, H. L., Chan, T. F., Wu, Y. H., Wu, Y. C., and Su, J. H. (2003) Arsenite-induced nitric oxide generation is cell cycle-dependent and aberrant in NBS cells. Toxicol. In Vitro 17, 139-143 (Pubitemid 36332234)
66. Kedersha, N., and Anderson, P. (2002) Stress granules: sites of mRNA triage that regulate mRNA stability and translatability. Biochem. Soc. Trans. 30, 963-969 (Pubitemid 36002389)