Evidence that the LRRK2 ROC domain Parkinson's disease-associated mutants A1442P and R1441C exhibit increased intracellular degradation

Journal of Neuroscience Research

Volumn 92, Issue 4, 2014, Pages 506-516

  Greene, Izabella D ^a   Mastaglia, Francis ^a   Meloni, Bruno P ^a,b   West, Kristin A ^a   Chieng, Joanne ^a   Mitchell, Chris J ^a   Gai, Wei Ping ^c   Boulos, Sherif ^a  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b SIR CHARLES GAIRDNER HOSPITAL   (Australia)

^c FLINDERS UNIVERSITY   (Australia)

Author keywords

A1442P; LRRK2; Parkinson's disease; R1441C; ROC domain mutations

Indexed keywords

A1442P; LRRK2; PARKINSON'S DISEASE; R1441C; ROC DOMAIN MUTATIONS;

AMINO ACIDS; ANALYSIS OF VARIANCE; CELL SURVIVAL; CYSTEINE PROTEINASE INHIBITORS; FLOW CYTOMETRY; GENE EXPRESSION REGULATION; GREEN FLUORESCENT PROTEINS; HEK293 CELLS; HUMANS; HYDROGEN PEROXIDE; LEUPEPTINS; MUTATION; PROTEIN-SERINE-THREONINE KINASES; TIME FACTORS; TRANSFECTION;

EID: 84895065892     PISSN: 03604012     EISSN: 10974547     Source Type: Journal    
DOI: 10.1002/jnr.23331     Document Type: Article

References (58)

1. Aasly JO, Vilarino-Guell C, Dachsel JC, Webber PJ, West AB, Haugarvoll K, Johansen KK, Toft M, Nutt JG, Payami H, Kachergus JM, Lincoln SJ, Felic A, Wider C, Soto-Ortolaza AI, Cobb SA, White LR, Ross OA, Farrer MJ. 2010. Novel pathogenic LRRK2 p.Asn1437His substitution in familial Parkinson's disease. Move Disord 25:2156-2163.
2. Alegre-Abarrategui J, Wade-Martins R. 2009. Parkinson disease, LRRK2 and the endocytic-autophagic pathway. Autophagy 5:1208-1210.
3. Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O, Wade-Martins R. 2009. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet 18:4022-4034.
4. Anand VS, Reichling LJ, Lipinski K, Stochaj W, Duan W, Kelleher K, Pungaliya P, Brown EL, Reinhart PH, Somberg R, Hirst WD, Riddle SM, Braithwaite SP. 2009. Investigation of leucine-rich repeat kinase 2: enzymological properties and novel assays. FEBS J 276:466-478.
5. 2+ entry through its constitutive and inducible movement in the endoplasmic reticulum. Proc Natl Acad Sci U S A 103:16704-16709.
6. Biskup S, Moore DJ, Rea A, Lorenz-Deperieux B, Coombes CE, Dawson VL, Dawson TM, West AB. 2007. Dynamic and redundant regulation of LRRK2 and LRRK1 expression. BMC Neurosci 8:102.
7. Deng J, Lewis PA, Greggio E, Sluch E, Beilina A, Cookson MR. 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.
8. Devine MJ, Kaganovich A, Ryten M, Mamais A, Trabzuni D, Manzoni C, McGoldrick P, Chan D, Dillman A, Zerle J, Horan S, Taanman JW, Hardy J, Marti-Masso JF, Healey D, Schapira AH, Wolozin B, Bandopadhyay R, Cookson MR, van der Brug MP, Lewis PA. 2011. Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue. Plos One 6(7).
9. Ding X, Goldberg MS. 2009. Regulation of LRRK2 stability by the E3 ubiquitin ligase CHIP. PLoS One 4:e5949.
10. Floris G, Cannas A, Solla P, Murru MR, Tranquilli S, Corongiu D, Rolesu M, Cuccu S, Sardu C, Marrosu F, Marrosu MG. 2009. Genetic analysis for five LRRK2 mutations in a Sardinian parkinsonian population: importance of G2019S and R1441C mutations in sporadic Parkinson's disease patients. Parkinsonism Rel Disord 15:277-280.
11. Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F. 2002. A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann Neurol 51:296-301.
12. Gaig C, Ezquerra M, Marti MJ, Munoz E, Valldeoriola F, Tolosa E. 2006. LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance. Arch Neurol 63:377-382.
13. Gaig C, Ezquerra M, Marti MJ, Valldeoriola F, Munoz E, Llado A, Rey MJ, Cardozo A, Molinuevo JL, Tolosa E. 2008. Screening for the LRRK2 G2019S and codon-1441 mutations in a pathological series of parkinsonian syndromes and frontotemporal lobar degeneration. J Neurol Sci 270:94-98.
14. Gardet A, Benita Y, Ballester I, Sands B, Korzenik J, Daly M, Xavier R, Podolsky D. 2010. LRRK2 is an interferon-gamma target involved in immune responses. Clin Immunol 135:S56-S56.
15. Gillardon F. 2009a. Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability-a point of convergence in parkinsonian neurodegeneration? J Neurochem 110:1514-1522.
16. Gillardon F. 2009b. Interaction of elongation factor 1-alpha with leucine-rich repeat kinase 2 impairs kinase activity and microtubule bundling in vitro. Neuroscience 163:533-539.
17. Gillardon F, Schmid R, Draheim H. 2012. Parkinson's disease-linked leucine-rich repeat kinase 2 (R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity. Neuroscience 208:41-48.
18. Greggio E, Cookson MR. 2009. Leucine-rich repeat kinase 2 mutations and Parkinson's disease: three questions. ASN Neuro 1(1).
19. Greggio E, Jain S, Kingsbury A, Bandopadhyay R, Lewis P, Kaganovich A, van der Brug MP, Beilina A, Blackinton J, Thomas KJ, Ahmad R, Miller DW, Kesavapany S, Singleton A, Lees A, Harvey RJ, Harvey K, Cookson MR. 2006. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol Dis 23:329-341.
20. Hakimi M, Selvanantham T, Swinton E, Padmore RF, Tong Y, Kabbach G, Venderova K, Girardin SE, Bulman DE, Scherzer CR, LaVoie MJ, Gris D, Park DS, Angel JB, Shen J, Philpott DJ, Schlossmacher MG. 2011. Parkinson's disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures. J Neural Transm 118:795-808.
21. Herzig MC, Kolly C, Persohn E, Theil D, Schweizer T, Hafner T, Stemmelen C, Troxler TJ, Schmid P, Danner S, Schnell CR, Mueller M, Kinzel B, Grevot A, Bolognani F, Stirn M, Kuhn RR, Kaupmann K, van der Putten PH, Rovelli G, Shimshek DR. 2011. LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice. Hum Mol Genet 20:4209-4223.
22. Herzig MC, Bidinosti M, Schweizer T, Hafner T, Stemmelen C, Weiss A, Danner S, Vidotto N, Stauffer D, Barske C, Mayer F, Schmid P, Rovelli G, van der Putten PH, Shimshek DR. 2012. High LRRK2 levels fail to induce or exacerbate neuronal alpha-synucleinopathy in mouse brain. PLoS One 7:e36581.
23. Higashi S, Moore DJ, Colebrooke RE, Biskup S, Dawson VL, Arai H, Dawson TM, Emson PC. 2007. Expression and localization of Parkinson's disease-associated leucine-rich repeat kinase 2 in the mouse brain. J Neurochem 100:368-381.
24. Huang Y, Halliday GM, Vandebona H, Mellick GD, Mastaglia F, Stevens J, Kwok J, Garlepp M, Silburn PA, Horne MK, Kotschet K, Venn A, Rowe DB, Rubio JP, Sue CM. 2007. Prevalence and clinical features of common LRRK2 mutations in Australians with Parkinson's disease. Mov Disord 22:982-989.
25. Jaleel M, Nichols RJ, Deak M, Campbell DG, Gillardon F, Knebel A, Alessi DR. 2007. LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity. Biochem J 405:307-317.
26. Kim B, Yang MS, Choi D, Kim JH, Kim HS, Seol W, Jou I, Kim EY, Joe E. 2011. Impaired inflammatory responses in murine Lrrk2-knockdown brain microglia. Glia 59:S141-S142.
27. Ko HS, Bailey R, Smith WW, Liu Z, Shin JH, Lee YI, Zhang YJ, Jiang H, Ross CA, Moore DJ, Patterson C, Petrucelli L, Dawson TM, Dawson VL. 2009. CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. Proc Natl Acad Sci U S A 106:2897-2902.
28. Li Y, Dunn L, Greggio E, Krumm B, Jackson GS, Cookson MR, Lewis PA, Deng J. 2009. The R1441C mutation alters the folding properties of the ROC domain of LRRK2. Biochim Biophys Acta 1792:1194-1197.
29. Liou AK, Leak RK, Li L, Zigmond MJ. 2008. Wild-type LRRK2 but not its mutant attenuates stress-induced cell death via ERK pathway. Neurobiol Dis 32:116-124.
30. Liu Z, Lee J, Krummey S, Lu W, Cai H, Lenardo MJ. 2011. The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nat Immunol 12:1063-1070.
31. Milosevic J, Schwarz SC, Ogunlade V, Meyer AK, Storch A, Schwarz J. 2009. Emerging role of LRRK2 in human neural progenitor cell cycle progression, survival and differentiation. Mol Neurodegen 4:25.
32. Moehle MS, Webber PJ, Tse T, Sukar N, Standaert DG, DeSilva TM, Cowell RM, West AB. 2011. LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci 32:1602-1611.
33. Mutez E, Larvor L, Lepretre F, Mouroux V, Hamalek D, Kerckaert JP, Perez-Tur J, Waucquier N, Vanbesien-Mailliot C, Duflot A, Devos D, Defebvre L, Kreisler A, Frigard B, Destee A, Chartier-Harlin MC. 2011. Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation. Neurobiol Aging 32:1839-1848.
34. Newman JR, Ghaemmaghami S, Ihmels J, Breslow DK, Noble M, DeRisi JL, Weissman JS. 2006. Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature 441:840-846.
35. Nichols RJ, Dzamko N, Morrice NA, Campbell DG, Deak M, Ordureau A, Macartney T, Tong Y, Shen J, Prescott AR, Alessi DR. 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.
36. Nuytemans K, Rademakers R, Theuns J, Pals P, Engelborghs S, Pickut B, de Pooter T, Peeters K, Mattheijssens M, Van den Broeck M, Cras P, De Deyn PP, van Broeckhoven C. 2008. Founder mutation p.R1441C in the leucine-rich repeat kinase 2 gene in Belgian Parkinson's disease patients. Eur J Hum Genet 16:471-479.
37. Nuytemans K, Theuns J, Cruts M, Van Broeckhoven C. 2010. Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum Mutat 31:763-780.
38. Ohta E, Katayama Y, Kawakami F, Yamamoto M, Tajima K, Maekawa T, Iida N, Hattori S, Obata F. 2009. I(2020)T leucine-rich repeat kinase 2, the causative mutant molecule of familial Parkinson's disease, has a higher intracellular degradation rate than the wild-type molecule. Biochem Biophys Res Commun 390:710-715.
39. Ohta E, Kubo M, Obata F. 2010. Prevention of intracellular degradation of I2020T mutant LRRK2 restores its protectivity against apoptosis. Biochem Biophys Res Commun 391:242-247.
40. Ozelius LJ, Senthil G, Saunders-Pullman R, Ohmann E, Deligtisch A, Tagliati M, Hunt AL, Klein C, Henick B, Hailpern SM, Lipton RB, Soto-Valencia J, Risch N, Bressman SB. 2006. LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N Engl J Med 354:424-425.
41. Paisán-Ruíz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-Tur J, Wood NW, Singleton AB. 2004. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44:595-600.
42. Plowey ED, Cherra SJ 3rd, Liu YJ, Chu CT. 2008. Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. J Neurochem 105:1048-1056.
43. Prinz M, Priller J, Sisodia SS, Ransohoff RM. 2011. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat Neurosci 14:1227-1235.
44. Ross OA, Spanaki C, Griffith A, Lin CH, Kachergus J, Haugarvoll K, Latsoudis H, Plaitakis A, Ferreira JJ, Sampaio C, Bonifati V, Wu RM, Zabetian CP, Farrer MJ. 2009. Haplotype analysis of Lrrk2 R1441H carriers with parkinsonism. Parkinsonism Rel Disord 15:466-467.
45. Sancho RM, Law BM, Harvey K. 2009. Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways. Hum Mol Genet 18:3955-3968.
46. Shin N, Jeong H, Kwon J, Heo HY, Kwon JJ, Yun HJ, Kim CH, Han BS, Tong Y, Shen J, Hatano T, Hattori N, Kim KS, Chang S, Seol W. 2008. LRRK2 regulates synaptic vesicle endocytosis. Exp Cell Res 314:2055-2065.
47. Smith WW, Pei Z, Jiang HB, Moore DJ, Liang YD, West AB, Dawson VL, Dawson TM, Ross CA. 2005. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci U S A 102:18676-18681.
48. Tansey MG, Goldberg MS. 2010. Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis 37:510-518.
49. Thévenet J, Gobert RP, van Huijsduijnen RH, Wiessner C, Sagot YJ. 2011. Regulation of LRRK2 expression points to a functional role in human monocyte maturation. Plos One 6(6).
50. Tong Y, Pisani A, Martella G, Karouani M, Yamaguchi H, Pothos EN, Shen J. 2009. R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc Natl Acad Sci U S A 106:14622-14627.
51. Tong YR, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher RJ, Shen J. 2010. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci U S A 107:9879-9884.
52. Tong YR, Giaime E, Yamaguchi H, Ichimura T, Liu YM, Si HQ, Cai HB, Bonventre JV, Shen J. 2012. Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway. Mol Neurodegen 7.
53. Wang L, Xie C, Greggio E, Parisiadou L, Shim H, Sun L, Chandran J, Lin X, Lai C, Yang WJ, Moore DJ, Dawson TM, Dawson VL, Chiosis G, Cookson MR, Cai H. 2008. The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2. J Neurosci 28:3384-3391.
54. Waxman EA, Covy JP, Bukh I, Li X, Dawson TM, Giasson BI. 2009. Leucine-rich repeat kinase 2 expression leads to aggresome formation that is not associated with alpha-synuclein inclusions. J Neuropathol Exp Neurol 68:785-796.
55. Webber PJ, West AB. 2009. LRRK2 in Parkinson's disease: function in cells and neurodegeneration. FEBS J 276:6436-6444.
56. West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM. 2005. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A 102:16842-16847.
57. Westerlund M, Belin AC, Anvret A, Bickford P, Olson L, Galter D. 2008. Developmental regulation of leucine-rich repeat kinase 1 and 2 expression in the brain and other rodent and human organs: implications for Parkinson's disease. Neuroscience 152:429-436.
58. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Muller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T. 2004. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44:601-607.