LRRK2 in Parkinson's disease: In vivo models and approaches for understanding pathogenic roles

FEBS Journal

Volumn 276, Issue 22, 2009, Pages 6445-6454

  Yue, Zhenyu ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Animal models; BAC transgenics; Dopamine; GTPase; Kinase; Leucine rich repeat kinase 2 (LRRK2); Parkinson's disease; Pathogenesis; ROCO

Indexed keywords

LEUCINE RICH REPEAT KINASE 2; PROTEIN; ROCO PROTEIN; UNCLASSIFIED DRUG;

BACTERIAL ARTIFICIAL CHROMOSOME; CAENORHABDITIS ELEGANS; CELL LOSS; DICTYOSTELIUM DISCOIDEUM; DOPAMINERGIC NERVE CELL; DROSOPHILA; DROSOPHILA MELANOGASTER; GENE MUTATION; HUMAN; IN VIVO STUDY; KNOCKOUT MOUSE; MOULD; NEMATODE; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; SHORT SURVEY; TRANSGENIC MOUSE;

ANIMALS; DROSOPHILA; HUMANS; MUTATION; MYXOMYCETES; PARKINSON DISEASE; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION;

ANIMALIA; INVERTEBRATA; MAMMALIA;

EID: 70350461833     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2009.07343.x     Document Type: Short Survey

References (47)

1. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB et al. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601 607.
2. Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Gil AM, Khan N et al. (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44, 595 600.
3. Healy DG, Falchi M, O'Sullivan SS, Bonifati V, Durr A, Bressman S, Brice A, Aasly J, Zabetian CP, Goldwurm S et al. (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol 7, 583 590.
4. Ozelius LJ, Senthil G, Saunders-Pullman R, Ohmann E, Deligtisch A, Tagliati M, Hunt AL, Klein C, Henick B, Hailpern SM et al. (2006) LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N Engl J Med 354, 424 425.
5. Bosgraaf L Van Haastert PJ (2003) Roc, a Ras/GTPase domain in complex proteins. Biochim Biophys Acta 1643, 5 10.
6. Marin I (2006) The Parkinson disease gene LRRK2: evolutionary and structural insights. Mol Biol Evol 23, 2423 2433.
7. 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 USA 102, 16842 16847.
8. Gloeckner CJ, Kinkl N, Schumacher A, Braun RJ, O'Neill E, Meitinger T, Kolch W, Prokisch H Ueffing M (2006) The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum Mol Genet 15, 223 232.
9. Smith WW, Pei Z, Jiang H, Dawson VL, Dawson TM Ross CA (2006) Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat Neurosci 9, 1231 1233.
10. Ito G, Okai T, Fujino G, Takeda K, Ichijo H, Katada T Iwatsubo T (2007) GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. Biochemistry 46, 1380 1388.
11. Li X, Tan YC, Poulose S, Olanow CW, Huang XY Yue Z (2007) Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants. J Neurochem 103, 238 247.
12. Guo L, Gandhi PN, Wang W, Petersen RB, Wilson-Delfosse AL Chen SG (2007) The Parkinson's disease-associated protein, leucine-rich repeat kinase 2 (LRRK2), is an authentic GTPase that stimulates kinase activity. Exp Cell Res 313, 3658 3670.
13. Smith WW, Pei Z, Jiang H, Moore DJ, Liang Y, 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 USA 102, 18676 18681.
14. Greggio E, Jain S, Kingsbury A, Bandopadhyay R, Lewis P, Kaganovich A, van der Brug MP, Beilina A, Blackinton J, Thomas KJ et al. (2006) Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol Dis 23, 329 341.
15. MacLeod D, Dowman J, Hammond R, Leete T, Inoue K Abeliovich A (2006) The familial Parkinsonism gene LRRK2 regulates neurite process morphology. Neuron 52, 587 593.
16. van Egmond WN, Kortholt A, Plak K, Bosgraaf L, Bosgraaf S, Keizer-Gunnink I van Haastert PJ (2008) Intramolecular activation mechanism of the Dictyostelium LRRK2 homolog Roco protein GbpC. J Biol Chem 283, 30412 30420.
17. Abysalh JC, Kuchnicki LL Larochelle DA (2003) The identification of pats1, a novel gene locus required for cytokinesis in Dictyostelium discoideum. Mol Biol Cell 14, 14 25.
18. Gotthardt K, Weyand M, Kortholt A, Van Haastert PJ 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, 2352.
19. West AB, Moore DJ, Choi C, Andrabi SA, Li X, Dikeman D, Biskup S, Zhang Z, Lim KL, Dawson VL et al. (2007) Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum Mol Genet 16, 223 232.
20. Bosgraaf L, Russcher H, Smith JL, Wessels D, Soll DR Van Haastert PJ (2002) A novel cGMP signalling pathway mediating myosin phosphorylation and chemotaxis in Dictyostelium. EMBO J 21, 4560 4570.
21. Bosgraaf L, Waijer A, Engel R, Visser AJ, Wessels D, Soll D van Haastert PJ (2005) RasGEF-containing proteins GbpC and GbpD have differential effects on cell polarity and chemotaxis in Dictyostelium. J Cell Sci 118, 1899 1910.
22. Dachsel JC, Taylor JP, Mok SS, Ross OA, Hinkle KM, Bailey RM, Hines JH, Szutu J, Madden B, Petrucelli L et al. (2007) Identification of potential protein interactors of Lrrk2. Parkinsonism Relat Disord 13, 382 385.
23. Gandhi PN, Wang X, Zhu X, Chen SG Wilson-Delfosse AL (2008) The Roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubules. J Neurosci Res 86, 1711 1720.
24. 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.
25. Sakaguchi-Nakashima A, Meir JY, Jin Y, Matsumoto K Hisamoto N (2007) LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins. Curr Biol 17, 592 598.
26. Wolozin B, Saha S, Guillily M, Ferree A Riley M (2008) Investigating convergent actions of genes linked to familial Parkinson's disease. Neurodegener Dis 5, 182 185.
27. Samann J, Hegermann J, von Gromoff E, Eimer S, Baumeister R Schmidt E (2009) Caenorhabditits elegans LRK-1 and PINK-1 act antagonistically in stress response and neurite outgrowth. J Biol Chem 284, 16482 16491.
28. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG et al. (2004) Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304, 1158 1160.
29. Lee SB, Kim W, Lee S Chung J (2007) Loss of LRRK2/PARK8 induces degeneration of dopaminergic neurons in Drosophila. Biochem Biophys Res Commun 358, 534 539.
30. Wang D, Tang B, Zhao G, Pan Q, Xia K, Bodmer R Zhang Z (2008) Dispensable role of Drosophila ortholog of LRRK2 kinase activity in survival of dopaminergic neurons. Mol Neurodegener 3, 3.
31. Imai Y, Gehrke S, Wang HQ, Takahashi R, Hasegawa K, Oota E Lu B (2008) Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. EMBO J 27, 2432 2443.
32. Liu Z, Wang X, Yu Y, Li X, Wang T, Jiang H, Ren Q, Jiao Y, Sawa A, Moran T et al. (2008) A Drosophila model for LRRK2-linked parkinsonism. Proc Natl Acad Sci USA 105, 2693 2698.
33. Li Y, Liu W, Oo TF, Wang L, Tang Y, Jackson-Lewis V, Zhou C, Geghman K, Bogdanov M, Przedborski S et al. (2009) Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat Neurosci 12, 826 828.
34. 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.
35. Westerlund M, Ran C, Borgkvist A, Sterky FH, Lindqvist E, Lundstromer K, Pernold K, Brene S, Kallunki P, Fisone G et al. (2008) Lrrk2 and alpha-synuclein are co-regulated in rodent striatum. Mol Cell Neurosci 39, 586 591.
36. Galter D, Westerlund M, Carmine A, Lindqvist E, Sydow O Olson L (2006) LRRK2 expression linked to dopamine-innervated areas. Ann Neurol 59, 714 719.
37. Melrose H, Lincoln S, Tyndall G, Dickson D Farrer M (2006) Anatomical localization of leucine-rich repeat kinase 2 in mouse brain. Neuroscience 139, 791 794.
38. Higashi S, Biskup S, West AB, Trinkaus D, Dawson VL, Faull RL, Waldvogel HJ, Arai H, Dawson TM, Moore DJ et al. (2007) Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain. Brain Res 1155, 208 219. (Pubitemid 46900930)
39. Simon-Sanchez J, Herranz-Perez V, Olucha-Bordonau F Perez-Tur J (2006) LRRK2 is expressed in areas affected by Parkinson's disease in the adult mouse brain. Eur J Neurosci 23, 659 666.
40. Taymans JM, Van den Haute C Baekelandt V (2006) Distribution of PINK1 and LRRK2 in rat and mouse brain. J Neurochem 98, 951 961.
41. Wang L, Xie C, Greggio E, Parisiadou L, Shim H, Sun L, Chandran J, Lin X, Lai C, Yang WJ et al. (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.
42. Melrose HL, Kent CB, Taylor JP, Dachsel JC, Hinkle KM, Lincoln SJ, Mok SS, Culvenor JG, Masters CL, Tyndall GM et al. (2007) A comparative analysis of leucine-rich repeat kinase 2 (Lrrk2) expression in mouse brain and Lewy body disease. Neuroscience 147, 1047 1058.
43. Antoch MP, Song EJ, Chang AM, Vitaterna MH, Zhao Y, Wilsbacher LD, Sangoram AM, King DP, Pinto LH Takahashi JS (1997) Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell 89, 655 667.
44. Heintz N (2001) BAC to the future: the use of bac transgenic mice for neuroscience research. Nat Rev Neurosci 2, 861 870.
45. Gong S, Zheng C, Doughty ML, Losos K, Didkovsky N, Schambra UB, Nowak NJ, Joyner A, Leblanc G, Hatten ME et al. (2003) A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425, 917 925.
46. Gray M, Shirasaki DI, Cepeda C, Andre VM, Wilburn B, Lu XH, Tao J, Yamazaki I, Li SH, Sun YE et al. (2008) Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci 28, 6182 6195.
47. Melrose H (2008) Update on the functional biology of Lrrk2. Future Neurol 3, 669 681.