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Centrosomal cohesion deficits as cellular biomarker in lymphoblastoid cell lines from LRRK2 Parkinson's disease patients

Fernández, Belén, Lara Ordóñez, Antonio Jesús, Fdez, Elena, Mutez, Eugénie, Comptdaer, Thomas, Leghay, Coline, Kreisler, Alexandre, Simonin, Clémence, Vandewynckel, Laurine, Defebvre, Luc, Destée, Alain, Bleuse, Séverine, Taymans, Jean-Marc, Chartier-Harlin, Marie-Christine, Hilfiker, Sabine·2019·Biochemical Journal
DOI 10.1042/bcj20190315PMC PMC6792036
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Abstract

Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for the treatment of Parkinson's disease (PD), and orally bioavailable, brain penetrant and highly potent LRRK2 kinase inhibitors are in early stages of clinical testing. Detection of LRRK2 phosphorylation, as well as phosphorylation of Rab10, a LRRK2 kinase substrate, have been proposed as target engagement biomarkers for LRRK2 inhibitor clinical trials. However, these readouts do not seem able to stratify patients based on enhanced LRRK2 kinase activity. Here, we describe a robust cell biological assay based on centrosomal cohesion alterations which were observed in peripheral blood mononuclear cell-derived lymphoblastoid cell lines (LCLs) from patients with G2019S LRRK2 mutations as compared with healthy controls, and could also be detected in a subset of sporadic PD patient samples. We suggest that LCLs may be a valuable resource for LRRK2 research, and that determination of centrosomal cohesion deficits may assist in the stratification of a subset of sporadic PD patients.

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  1. 2015, Parkinson's disease, Lancet, 386, 896, 10.1016/S0140-6736(14)61393-3 · DOI · Paper page
  2. 2015, Snapshot: genetics of Parkinson's disease, Cell, 160, 570, 10.1016/j.cell.2015.01.019 · DOI
  3. 2008, Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study, Lancet Neurol., 7, 583, 10.1016/S1474-4422(08)70117-0 · DOI · Paper page
  4. 2005, A common LRRK2 mutation in idiopathic Parkinson's disease, Lancet, 365, 415, 10.1016/S0140-6736(05)17830-1 · DOI · Paper page
  5. 2011, Genetic characteristics of leucine-rich repeat kinase 2 (LRRK2) associated Parkinson's disease, Parkinsonism Relat. Disord., 17, 501, 10.1016/j.parkreldis.2010.11.008 · DOI
  6. 2013, Fine-mapping, gene expression and splicing analysis of the disease associated LRRK2 locus, PLoS ONE, 8, e70724, 10.1371/journal.pone.0070724 · DOI
  7. 2018, The role of monogenic genes in idiopathic Parkinson's disease, Neurobiol. Dis., 124, 230, 10.1016/j.nbd.2018.11.012 · DOI
  8. 2018, LRRK2 kinase in Parkinson's disease, Science, 360, 36, 10.1126/science.aar5683 · DOI · Paper page
  9. 2009, Leucine-rich repeat kinase 2 mutations and Parkinson's disease: three questions, ASN Neuro, 1, e00002, 10.1042/AN20090007 · DOI
  10. 2016, Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases, eLife, 5, e12813, 10.7554/eLife.12813 · DOI · Paper page
  11. 2016, LRRK2 kinase inhibition as a therapeutic strategy for Parkinson's disease, where do we stand?, Curr. Neuropharmacol., 14, 214, 10.2174/1570159X13666151030102847 · DOI
  12. 2017, Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson's disease, Exp. Neurol., 298, 236, 10.1016/j.expneurol.2017.07.019 · DOI
  13. 2017, Mechanisms of mutant LRRK2 neurodegeneration, Adv. Neurobiol., 14, 227, 10.1007/978-3-319-49969-7_12 · DOI
  14. 2004, Regulation of protein kinases; controlling activity through activation segment conformation, Mol. Cell, 15, 661, 10.1016/j.molcel.2004.08.024 · DOI
  15. 2012, Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations, Sci. Transl. Med., 4, 164ra161, 10.1126/scitranslmed.3004485 · DOI
  16. 2010, 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization, Biochem. J., 430, 393, 10.1042/BJ20100483 · DOI
  17. 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, 10.1042/BJ20100784 · DOI
  18. 2014, Lack of correlation between the kinase activity of LRRK2 harboring kinase-modifying mutations and its phosphorylation at Ser910, 935 and Ser955, PLoS ONE, 9, e97988, 10.1371/journal.pone.0097988 · DOI
  19. 2017, GTP binding regulates cellular localization of Parkinson's disease-associated LRRK2, Hum. Mol. Genet., 26, 2747, 10.1093/hmg/ddx161 · DOI
  20. 2014, In silico, in vitro and cellular analysis with a kinome-wide inhibitor panel correlates cellular LRRK2 dephosphorylation to inhibitor activity on LRRK2, Front. Mol. Neurosci., 7, 51, 10.3389/fnmol.2014.00051 · DOI
  21. 2013, Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle, Biochem. J., 456, 119, 10.1042/BJ20121772 · DOI
  22. 2017, Small-molecule inhibitors of LRRK2, Adv. Neurobiol., 14, 241, 10.1007/978-3-319-49969-7_13 · DOI · Paper page
  23. 2016, Inhibitor treatment of peripheral mononuclear cells from Parkinson's disease patients further validates LRRK2 dephosphorylation as a pharmacodynamic biomarker, Sci. Rep., 6, 31391, 10.1038/srep31391 · DOI
  24. 2013, Measurement of LRRK2 and Ser910/935 phosphorylated LRRK2 in peripheral blood mononuclear cells from idiopathic Parkinson's disease patients, J. Parkinson’s Dis., 3, 145, 10.3233/JPD-130174 · DOI
  25. 2017, Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis, eLife, 6, e31012, 10.7554/eLife.31012 · DOI · Paper page
  26. 2017, Selective LRRK2 kinase inhibition reduces phosphorylation of endogenous Rab10 and Rab12 in human peripheral mononuclear blood cells, Sci. Rep., 7, 10300, 10.1038/s41598-017-10501-z · DOI
  27. 2018, Dysregulated phosphorylation of Rab GTPases by LRRK2 induces neurodegeneration, Mol. Neurodegener., 13, 8, 10.1186/s13024-018-0240-1 · DOI
  28. 2018, Development of phospho-specific Rab protein antibodies to monitor in vivo activity of the LRRK2 Parkinson's disease kinase, Biochem. J., 475, 1, 10.1042/BCJ20170802 · DOI · Paper page
  29. 2018, Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils, Biochem. J., 475, 23, 10.1042/BCJ20170803 · DOI · Paper page
  30. 2018, LRRK2-mediated rab10 phosphorylation in immune cells from Parkinson's disease patients, Mov. Disord., 34, 406, 10.1002/mds.27601 · DOI · Paper page
  31. 2018, Parkinson disease-associated mutations in LRRK2 cause centrosomal defects via Rab8a phosphorylation, Mol. Neurodener., 13, 3, 10.1186/s13024-018-0235-y · DOI
  32. 2009, The leucine rich repeat kinase 2 (LRRK2) G2019S substitution mutation. Association with Parkinson disease, malignant melanoma and prevalence in ethnic groups in Israel, J. Neurol., 256, 483, 10.1007/s00415-009-0117-x · DOI
  33. 1991, A novel approach to establishing permanent lymphoblastoid cell lines: Epstein-Barr virus transformation of cryopreserved lymphocytes, Am. J. Hum. Genet., 48, 637
  34. 2018, LRRK2 activation in idiopathic Parkinson's disease, Sci. Transl. Med., 10, eaar5429, 10.1126/scitranslmed.aar5429 · DOI
  35. 2011, The centrosome cycle: centriole biogenesis, duplication and inherent asymmetries, Nat. Cell. Biol., 13, 1154, 10.1038/ncb2345 · DOI
  36. 2018, Reduced LRRK2 in association with retromer dysfunction in post-mortem brain tissue from LRRK2 mutation carriers, Brain, 141, 486, 10.1093/brain/awx344 · DOI · Paper page
  37. 2018, Rab29 activation of the Parkinson's disease-associated LRRK2 kinase, EMBO J., 37, 1, 10.15252/embj.201798099 · DOI · Paper page
  38. 2018, LRRK2 phosphorylates membrane-bound Rabs and is activated by GTP-bound Rab7L1 to promote recruitment to the trans-Golgi network, Hum. Mol. Genet., 27, 385, 10.1093/hmg/ddx410 · DOI · Paper page
  39. 2018, Rab7L1-mediated relocalization of LRRK2 to the Golgi complex causes centrosomal deficits via Rab8a, Front. Mol. Neurosci., 11, 417, 10.3389/fnmol.2018.00417 · DOI · Paper page
  40. 2018, The Parkinson's disease VPS35[D620N] mutation enhances LRRK2-mediated Rab protein phosphorylation in mouse and human, Biochem. J., 475, 1861, 10.1042/BCJ20180248 · DOI · Paper page

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Metadata

Authors
Fernández, B., Lara Ordóñez, A. J., Fdez, E., Mutez, E., Comptdaer, T., Leghay, C., Kreisler, A., Simonin, C., Vandewynckel, L., Defebvre, L., Destée, A., Bleuse, S., Taymans, J.-M., Chartier-Harlin, M.-C., & Hilfiker, S.
Affiliations
  • Consejo Superior de Investigaciones Científicas (CSIC), Institute of Parasitology and Biomedicine ‘López-Neyra’, Avda del Conocimiento s/n, 18016 Granada, Spain
  • Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre Aubert Neurosciences et Cancer, University of Lille, F-59000 Lille, France
  • Neurology and Movement Disorders Department, Centre Hospitalier Universitaire Lille, Lille, France
ORCID
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
2019-10-11
Volume
476
Issue
19
Pages
2797-2813
ISSN
  • 0264-6021
  • 1470-8728
DOI
10.1042/bcj20190315
PMC
PMC6792036
Cited by
37
References
4
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)

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