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Molecular Insights and Functional Implication of LRRK2 Dimerization

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Leucine-Rich Repeat Kinase 2 (LRRK2)

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 14))

Abstract

The Parkinson’s disease protein leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein with an enzymatic core comprising serine-threonine kinase and GTPase activities and a number of protein-protein interaction domains. While the complex domain architecture of LRRK2 has hampered its structural investigation, there is convincing evidence that LRRK2 can form dimers in solution and in the cell and that the GTPase/ROC domain plays a central role in this process. This chapter focuses on recent studies addressing the molecular nature, the functional significance, and the pathological implication of LRRK2 dimerization.

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References

  1. Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141(7):1117–1134. doi:10.1016/j.cell.2010.06.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lavoie H, Therrien M (2015) Regulation of RAF protein kinases in ERK signalling. Nat Rev Mol Cell Biol 16(5):281–298. doi:10.1038/nrm3979

    Article  CAS  PubMed  Google Scholar 

  3. Parrini MC, Lei M, Harrison SC, Mayer BJ (2002) Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1. Mol Cell 9(1):73–83

    Article  CAS  PubMed  Google Scholar 

  4. Civiero L, Dihanich S, Lewis PA, Greggio E (2014) Genetic, structural, and molecular insights into the function of ras of complex proteins domains. Chem Biol 21(7):809–818. doi:10.1016/j.chembiol.2014.05.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bosgraaf L, Van Haastert PJ (2003) Roc, a Ras/GTPase domain in complex proteins. Biochim Biophys Acta 1643(1–3):5–10

    Article  CAS  PubMed  Google Scholar 

  6. Gilsbach BK, Kortholt A (2014) Structural biology of the LRRK2 GTPase and kinase domains: implications for regulation. Front Mol Neurosci 7:32. doi:10.3389/fnmol.2014.00032

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gasper R, Meyer S, Gotthardt K, Sirajuddin M, Wittinghofer A (2009) It takes two to tango: regulation of G proteins by dimerization. Nat Rev Mol Cell Biol 10(6):423–429. doi:10.1038/nrm2689

    Article  CAS  PubMed  Google Scholar 

  8. Gilsbach BK, Ho FY, Vetter IR, van Haastert PJ, Wittinghofer A, Kortholt A (2012) Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations. Proc Natl Acad Sci U S A 109(26):10322–10327. doi:10.1073/pnas.1203223109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu Z, Mobley JA, DeLucas LJ, Kahn RA, West AB (2015) LRRK2 autophosphorylation enhances its GTPase activity. FASEB J 30:336–347. doi:10.1096/fj.15-277095

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gloeckner CJ, Schumacher A, Boldt K, Ueffing M (2009) The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro. J Neurochem 109(4):959–968. doi:10.1111/j.1471-4159.2009.06024.x

    Article  CAS  PubMed  Google Scholar 

  11. Civiero L, Vancraenenbroeck R, Belluzzi E, Beilina A, Lobbestael E, Reyniers L, Gao F, Micetic I, De Maeyer M, Bubacco L, Baekelandt V, Cookson MR, Greggio E, Taymans JM (2012) Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers. PLoS One 7(8), e43472. doi:10.1371/journal.pone.0043472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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(5):1499–1504. doi:10.1073/pnas.0709098105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liao J, Wu CX, Burlak C, Zhang S, Sahm H, Wang M, Zhang ZY, Vogel KW, Federici M, Riddle SM, Nichols RJ, Liu D, Cookson MR, Stone TA, Hoang QQ (2014) Parkinson disease-associated mutation R1441H in LRRK2 prolongs the “active state” of its GTPase domain. Proc Natl Acad Sci U S A 111(11):4055–4060. doi:10.1073/pnas.1323285111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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(16):2239–2249. doi:10.1038/emboj.2008.150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rudi K, Ho FY, Gilsbach BK, Pots H, Wittinghofer A, Kortholt A, Klare JP (2015) Conformational heterogeneity of the Roc domains in C. tepidum Roc-COR and implications for human LRRK2 Parkinson mutations. Biosci Rep 35(5), e00254. doi:10.1042/BSR20150128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Daniels V, Vancraenenbroeck R, Law BM, Greggio E, Lobbestael E, Gao F, De Maeyer M, Cookson MR, Harvey K, Baekelandt V, Taymans JM (2011) Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant. J Neurochem 116(2):304–315. doi:10.1111/j.1471-4159.2010.07105.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lewis PA, Greggio E, Beilina A, Jain S, Baker A, Cookson MR (2007) The R1441C mutation of LRRK2 disrupts GTP hydrolysis. Biochem Biophys Res Commun 357(3):668–671. doi:10.1016/j.bbrc.2007.04.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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(12):1194–1197. doi:10.1016/j.bbadis.2009.09.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Terheyden S, Ho FY, Gilsbach BK, Wittinghofer A, Kortholt A (2015) Revisiting the Roco G-protein cycle. Biochem J 465(1):139–147. doi:10.1042/BJ20141095

    Article  CAS  PubMed  Google Scholar 

  20. Sen S, Webber PJ, West AB (2009) Dependence of leucine-rich repeat kinase 2 (LRRK2) kinase activity on dimerization. J Biol Chem 284(52):36346–36356. doi:10.1074/jbc.M109.025437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Meyer S, Bohme S, Kruger A, Steinhoff HJ, Klare JP, Wittinghofer A (2009) Kissing G domains of MnmE monitored by X-ray crystallography and pulse electron paramagnetic resonance spectroscopy. PLoS Biol 7(10), e1000212. doi:10.1371/journal.pbio.1000212

    Article  PubMed  PubMed Central  Google Scholar 

  22. 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(2):223–232. doi:10.1093/hmg/ddi439

    Article  CAS  PubMed  Google Scholar 

  23. Greggio E, Zambrano I, Kaganovich A, Beilina A, Taymans JM, Daniels V, Lewis P, Jain S, Ding J, Syed A, Thomas KJ, Baekelandt V, Cookson MR (2008) The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation. J Biol Chem 283(24):16906–16914. doi:10.1074/jbc.M708718200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jorgensen ND, Peng Y, Ho CC, Rideout HJ, Petrey D, Liu P, Dauer WT (2009) The WD40 domain is required for LRRK2 neurotoxicity. PLoS One 4(12), e8463. doi:10.1371/journal.pone.0008463

    Article  PubMed  PubMed Central  Google Scholar 

  25. Klein CL, Rovelli G, Springer W, Schall C, Gasser T, Kahle PJ (2009) Homo—and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment. J Neurochem 111(3):703–715. doi:10.1111/j.1471-4159.2009.06358.x

    Article  CAS  PubMed  Google Scholar 

  26. Sheng Z, Zhang S, Bustos D, Kleinheinz T, Le Pichon CE, Dominguez SL, Solanoy HO, Drummond J, Zhang X, Ding X, Cai F, Song Q, Li X, Yue Z, van der Brug MP, Burdick DJ, Gunzner-Toste J, Chen H, Liu X, Estrada AA, Sweeney ZK, Scearce-Levie K, Moffat JG, Kirkpatrick DS, 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(164), 164ra161. doi:10.1126/scitranslmed.3004485

    Article  PubMed  Google Scholar 

  27. Cirnaru MD, Marte A, Belluzzi E, Russo I, Gabrielli M, Longo F, Arcuri L, Murru L, Bubacco L, Matteoli M, Fedele E, Sala C, Passafaro M, Morari M, Greggio E, Onofri F, Piccoli G (2014) LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter release through modulation of LRRK2 macro-molecular complex. Front Mol Neurosci 7:49. doi:10.3389/fnmol.2014.00049

    Article  PubMed  PubMed Central  Google Scholar 

  28. Rudenko IN, Kaganovich A, Hauser DN, Beylina A, Chia R, Ding J, Maric D, Jaffe H, Cookson MR (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(1):99–111. doi:10.1042/BJ20120637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lu B, Zhai Y, Wu C, Pang X, Xu Z, Sun F (2010) Expression, purification and preliminary biochemical studies of the N-terminal domain of leucine-rich repeat kinase 2. Biochim Biophys Acta 1804(9):1780–1784. doi:10.1016/j.bbapap.2010.05.004

    Article  CAS  PubMed  Google Scholar 

  30. Ito G, Iwatsubo T (2012) Re-examination of the dimerization state of leucine-rich repeat kinase 2: predominance of the monomeric form. Biochem J 441(3):987–994. doi:10.1042/BJ20111215

    Article  CAS  PubMed  Google Scholar 

  31. James NG, Digman MA, Gratton E, Barylko B, Ding X, Albanesi JP, Goldberg MS, Jameson DM (2012) Number and brightness analysis of LRRK2 oligomerization in live cells. Biophys J 102(11):L41–L43. doi:10.1016/j.bpj.2012.04.046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mamais A, Chia R, Beilina A, Hauser DN, Hall C, Lewis PA, Cookson MR, Bandopadhyay R (2014) Arsenite stress down-regulates phosphorylation and 14-3-3 binding of leucine-rich repeat kinase 2 (LRRK2), promoting self-association and cellular redistribution. J Biol Chem 289(31):21386–21400. doi:10.1074/jbc.M113.528463

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kett LR, Boassa D, Ho CC, Rideout HJ, Hu J, Terada M, Ellisman M, Dauer WT (2012) LRRK2 Parkinson disease mutations enhance its microtubule association. Hum Mol Genet 21(4):890–899. doi:10.1093/hmg/ddr526

    Article  CAS  PubMed  Google Scholar 

  34. Berger Z, Smith KA, Lavoie MJ (2010) Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation. Biochemistry 49(26):5511–5523. doi:10.1021/bi100157u

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schapansky J, Nardozzi JD, Felizia F, LaVoie MJ (2014) Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy. Hum Mol Genet 23(16):4201–4214. doi:10.1093/hmg/ddu138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tong Y, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher RJ 3rd, 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(21):9879–9884. doi:10.1073/pnas.1004676107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tong Y, Giaime E, Yamaguchi H, Ichimura T, Liu Y, Si H, Cai H, Bonventre JV, Shen J (2012) Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway. Mol Neurodegener 7:2. doi:10.1186/1750-1326-7-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Manzoni C, Mamais A, Dihanich S, Abeti R, Soutar MP, Plun-Favreau H, Giunti P, Tooze SA, Bandopadhyay R, Lewis PA (2013) Inhibition of LRRK2 kinase activity stimulates macroautophagy. Biochim Biophys Acta 1833(12):2900–2910. doi:10.1016/j.bbamcr.2013.07.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 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(3):393–404. doi:10.1042/BJ20100483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Holderfield M, Nagel TE, Stuart DD (2014) Mechanism and consequences of RAF kinase activation by small-molecule inhibitors. Br J Cancer 111(4):640–645. doi:10.1038/bjc.2014.139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dzamko N, Deak M, Hentati F, Reith AD, Prescott AR, Alessi DR, Nichols RJ (2010) Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization. Biochem J 430(3):405–413. doi:10.1042/BJ20100784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Li X, Wang QJ, Pan N, Lee S, Zhao Y, Chait BT, Yue Z (2011) Phosphorylation-dependent 14-3-3 binding to LRRK2 is impaired by common mutations of familial Parkinson’s disease. PLoS One 6(3), e17153. doi:10.1371/journal.pone.0017153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fu H, Subramanian RR, Masters SC (2000) 14-3-3 proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol 40:617–647. doi:10.1146/annurev.pharmtox.40.1.617

    Article  CAS  PubMed  Google Scholar 

  44. Bastea LI, Doppler H, Pearce SE, Durand N, Spratley SJ, Storz P (2013) Protein kinase D-mediated phosphorylation at Ser99 regulates localization of p21-activated kinase 4. Biochem J 455(2):251–260. doi:10.1042/BJ20130281

    Article  CAS  PubMed  Google Scholar 

  45. Lobbestael E, Zhao J, Rudenko IN, Beylina A, Gao F, Wetter J, Beullens M, Bollen M, Cookson MR, Baekelandt V, Nichols RJ, Taymans JM (2013) Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle. Biochem J 456(1):119–128. doi:10.1042/BJ20121772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chia R, Haddock S, Beilina A, Rudenko IN, Mamais A, Kaganovich A, Li Y, Kumaran R, Nalls MA, Cookson MR (2014) Phosphorylation of LRRK2 by casein kinase 1alpha regulates trans-Golgi clustering via differential interaction with ARHGEF7. Nat Commun 5:5827. doi:10.1038/ncomms6827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cookson MR (2010) The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson’s disease. Nat Rev Neurosci 11(12):791–797. doi:10.1038/nrn2935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Greggio E, Cookson MR (2009) Leucine-rich repeat kinase 2 mutations and Parkinson’s disease: three questions. ASN Neuro 1(1):13–24. doi:10.1042/AN20090007

    Article  CAS  Google Scholar 

  49. Ray S, Bender S, Kang S, Lin R, Glicksman MA, Liu M (2014) The Parkinson disease-linked LRRK2 protein mutation I2020T stabilizes an active state conformation leading to increased kinase activity. J Biol Chem 289(19):13042–13053. doi:10.1074/jbc.M113.537811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Doggett EA, Zhao J, Mork CN, Hu D, Nichols RJ (2012) Phosphorylation of LRRK2 serines 955 and 973 is disrupted by Parkinson’s disease mutations and LRRK2 pharmacological inhibition. J Neurochem 120(1):37–45. doi:10.1111/j.1471-4159.2011.07537.x

    Article  CAS  PubMed  Google Scholar 

  51. Beilina A, Rudenko IN, Kaganovich A, Civiero L, Chau H, Kalia SK, Kalia LV, Lobbestael E, Chia R, Ndukwe K, Ding J, Nalls MA, Olszewski M, Hauser DN, Kumaran R, Lozano AM, Baekelandt V, Greene LE, Taymans JM, Greggio E, Cookson MR (2014) Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc Natl Acad Sci U S A 111(7):2626–2631. doi:10.1073/pnas.1318306111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ohta E, Kawakami F, Kubo M, Obata F (2013) Dominant-negative effects of LRRK2 heterodimers: a possible mechanism of neurodegeneration in Parkinson’s disease caused by LRRK2 I2020T mutation. Biochem Biophys Res Commun 430(2):560–566. doi:10.1016/j.bbrc.2012.11.113

    Article  CAS  PubMed  Google Scholar 

  53. Miyajima T, Ohta E, Kawada H, Maekawa T, Obata F (2015) The mouse/human cross-species heterodimer of leucine-rich repeat kinase 2: possible significance in the transgenic model mouse of Parkinson’s disease. Neurosci Lett 588:142–146. doi:10.1016/j.neulet.2015.01.003

    Article  CAS  PubMed  Google Scholar 

  54. Liu M, Kang S, Ray S, Jackson J, Zaitsev AD, Gerber SA, Cuny GD, Glicksman MA (2011) Kinetic, mechanistic, and structural modeling studies of truncated wild-type leucine-rich repeat kinase 2 and the G2019S mutant. Biochemistry 50(43):9399–9408. doi:10.1021/bi201173d

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gilligan PJ (2015) Inhibitors of leucine-rich repeat kinase 2 (LRRK2): progress and promise for the treatment of Parkinson’s disease. Curr Top Med Chem 15(10):927–938

    Article  CAS  PubMed  Google Scholar 

  56. Fuji RN, Flagella M, Baca M, Baptista MA, Brodbeck J, Chan BK, Fiske BK, Honigberg L, Jubb AM, Katavolos P, Lee DW, Lewin-Koh SC, Lin T, Liu X, Liu S, Lyssikatos JP, O’Mahony J, Reichelt M, Roose-Girma M, Sheng Z, Sherer T, Smith A, Solon M, Sweeney ZK, Tarrant J, Urkowitz A, Warming S, Yaylaoglu M, Zhang S, Zhu H, Estrada AA, Watts RJ (2015) Effect of selective LRRK2 kinase inhibition on nonhuman primate lung. Sci Transl Med 7(273):273ra215. doi:10.1126/scitranslmed.aaa3634

    Article  Google Scholar 

  57. 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(21):4209–4223. doi:10.1093/hmg/ddr348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhao J, Molitor TP, Langston JW, Nichols RJ (2015) LRRK2 dephosphorylation increases its ubiquitination. Biochem J 469(1):107–120. doi:10.1042/BJ20141305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Daniels RH, Zenke FT, Bokoch GM (1999) alphaPix stimulates p21-activated kinase activity through exchange factor-dependent and -independent mechanisms. J Biol Chem 274(10):6047–6050

    Article  CAS  PubMed  Google Scholar 

  60. Loiarro M, Capolunghi F, Fanto N, Gallo G, Campo S, Arseni B, Carsetti R, Carminati P, De Santis R, Ruggiero V, Sette C (2007) Pivotal advance: inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. J Leukoc Biol 82(4):801–810. doi:10.1189/jlb.1206746

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by the Italian Telethon Foundation (grant n. GGP12237) and the Michael J Fox Foundation for Parkinson’s disease research.

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The author declares no conflicts of interest.

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Authors and Affiliations

  1. Department of Biology, University of Padova, Via Ugo Bassi 58/B, Padova, 35131, Italy

    Laura Civiero, Isabella Russo, Luigi Bubacco & Elisa Greggio

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  1. Laura Civiero
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  2. Isabella Russo
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  3. Luigi Bubacco
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  4. Elisa Greggio
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Correspondence to Elisa Greggio .

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  1. Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece

    Hardy J. Rideout

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Civiero, L., Russo, I., Bubacco, L., Greggio, E. (2017). Molecular Insights and Functional Implication of LRRK2 Dimerization. In: Rideout, H. (eds) Leucine-Rich Repeat Kinase 2 (LRRK2). Advances in Neurobiology, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-49969-7_6

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