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Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

Steger, Martin, Tonelli, Francesca, Ito, Genta, Davies, Paul, Trost, Matthias, Vetter, Melanie, Wachter, Stefanie, Lorentzen, Esben, Duddy, Graham, Wilson, Stephen, Baptista, Marco AS, Fiske, Brian K, Fell, Matthew J, Morrow, John A, Reith, Alastair D, Alessi, Dario R, Mann, Matthias·2016·eLife
DOI 10.7554/elife.12813PMC PMC4769169
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Abstract

Mutations in Park8, encoding for the multidomain Leucine-rich repeat kinase 2 (LRRK2) protein, comprise the predominant genetic cause of Parkinson's disease (PD). G2019S, the most common amino acid substitution activates the kinase two- to threefold. This has motivated the development of LRRK2 kinase inhibitors; however, poor consensus on physiological LRRK2 substrates has hampered clinical development of such therapeutics. We employ a combination of phosphoproteomics, genetics, and pharmacology to unambiguously identify a subset of Rab GTPases as key LRRK2 substrates. LRRK2 directly phosphorylates these both in vivo and in vitro on an evolutionary conserved residue in the switch II domain. Pathogenic LRRK2 variants mapping to different functional domains increase phosphorylation of Rabs and this strongly decreases their affinity to regulatory proteins including Rab GDP dissociation inhibitors (GDIs). Our findings uncover a key class of bona-fide LRRK2 substrates and a novel regulatory mechanism of Rabs that connects them to PD.

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  • Most mutations in LRRK2 increase its kinase activity, increasing phosphorylation of a broad subset of Rab GTPases.

    “Most mutations in LRRK2 increase its kinase activity, increasing phosphorylation of a broad subset of Rab GTPases [79].”

    From Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain (2023) · cites this paper as [79]

    The Introduction says that PD-associated LRRK2 mutations increase phosphorylation of at least three Rab GTPases, supporting increased phosphorylation of a subset, but not characterizing that subset as broad. The Results section on pathogenic mutations distinguishes kinase-domain mutations that augment kinase activity from the ROC-COR mutation R1441C, which increased Rab phosphorylation in cells without directly enhancing kinase activity. The paper therefore does not support the claim that most mutations increase kinase activity as the mechanism. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • pRab10 likely plays a role in neurodegenerative diseases including Parkinson's and Alzheimer's diseases.

    “Rab10 and its phosphorylated form, pRab10 likely play a role in neurodegenerative diseases including Parkinson’s and Alzheimer’s diseases [64, 79, 94].”

    From Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain (2023) · cites this paper as [79]

    The Results section, “Parkinson’s disease-associated pathogenic mutations modulate Rab GTPase phosphorylation levels” (page unavailable), reports that PD-associated LRRK2 mutations increased phosphorylated Rab10 in cells, supporting a possible Parkinson’s link. Our copy does not connect Rab10 or pRab10 to Alzheimer’s disease, so it does not support that part of the claim. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Several RABs identified as being controlled by Retromer are substrates for LRRK2-mediated phosphorylation in response to disrupted lysosomal homoeostasis.

    “several RABs identified as being controlled by Retromer are substrates for LRKK2-mediated phosphorylation in response to disrupted lysosomal homoeostasis127–129.”

    From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [129]

    The Results section, “Direct in vitro phosphorylation of Rab isoforms by LRRK2” (page unavailable), shows that LRRK2 phosphorylates several Rab GTPases, and the physiological-substrates section finds that only a subset are targets in cells. Our copy does not establish that these Rabs are controlled by Retromer or that disrupted lysosomal homeostasis triggers their phosphorylation; the Discussion mentions lysosomal-pathway defects in LRRK2-knockout animals but does not make that causal claim. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Rab10 is a LRRK2 kinase substrate.

    “Rab10 is a LRRK2 kinase substrate [79], therefore, immunofluorescence was performed to see if Rab10 and pRab10 are present in SPNs.”

    From Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain (2023) · cites this paper as [79]

  • Multiple studies show that a subset of Rab GTPases are LRRK2 kinase substrates, and LRRK2 can phosphorylate these Rab GTPases in vivo and in vitro.

    “Multiple studies show that a subset of Rab GTPases are LRRK2 kinase substrates, and LRRK2 can phosphorylate these Rab GTPases in vivo and in vitro [41, 79].”

    From Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain (2023) · cites this paper as [79]

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Research works printed but not linked: 80

  1. Bailey, 2013, LRRK2 phosphorylates novel tau epitopes and promotes tauopathy, Acta Neuropathologica, 126, 809, 10.1007/s00401-013-1188-4 · DOI
  2. Baptista, 2013, Loss of leucine-rich repeat kinase 2 (LRRK2) in rats leads to progressive abnormal phenotypes in peripheral organs, PLoS One, 8, e80705, 10.1371/journal.pone.0080705 · DOI
  3. Bleimling, 2009, Chaperone-assisted production of active human Rab8A GTPase in escherichia coli, Protein Expression and Purification, 65, 190, 10.1016/j.pep.2008.12.002 · DOI
  4. Burbulla, 2011, Converging environmental and genetic pathways in the pathogenesis of parkinson's disease, Journal of the Neurological Sciences, 306, 1, 10.1016/j.jns.2011.04.005 · DOI
  5. Campbell, 2002, Identification of protein phosphorylation sites by a combination of mass spectrometry and solid phase edman sequencing, Journal of Biomolecular Techniques, 13, 119
  6. Chaugule, 2011, Autoregulation of parkin activity through its ubiquitin-like domain, The EMBO Journal, 30, 2853, 10.1038/emboj.2011.204 · DOI · Paper page
  7. Chen, 2012, (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD, Cell Death and Differentiation, 19, 1623, 10.1038/cdd.2012.42 · DOI
  8. Choi, 2012, Brain penetrant LRRK2 inhibitor, ACS Medicinal Chemistry Letters, 3, 658, 10.1021/ml300123a · DOI
  9. Cookson, 2015, LRRK2 pathways leading to neurodegeneration, Current Neurology and Neuroscience Reports, 15, 42, 10.1007/s11910-015-0564-y · DOI
  10. Cooper, 2006, Alpha-synuclein blocks ER-golgi traffic and Rab1 rescues neuron loss in parkinson's models, Science, 313, 324, 10.1126/science.1129462 · DOI
  11. Cox, 2014, Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ, Molecular & Cellular Proteomics, 13, 2513, 10.1074/mcp.M113.031591 · DOI · Paper page
  12. Cox, 2008, MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification, Nature Biotechnology, 26, 1367, 10.1038/nbt.1511 · DOI · Paper page
  13. Cox, 2011, Andromeda: a peptide search engine integrated into the MaxQuant environment, Journal of Proteome Research, 10, 1794, 10.1021/pr101065j · DOI
  14. Davies, 2013, Comprehensive characterization and optimization of anti-LRRK2 (leucine-rich repeat kinase 2) monoclonal antibodies, Biochemical Journal, 453, 101, 10.1042/BJ20121742 · DOI
  15. Delprato, 2004, Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of rabex-5, Cell, 118, 607, 10.1016/j.cell.2004.08.009 · DOI
  16. Dzamko, 2010, Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser 910 /Ser 935 , disruption of 14-3-3 binding and altered cytoplasmic localization, Biochemical Journal, 430, 405, 10.1042/BJ20100784 · DOI
  17. Dzamko, 2012, The IkappaB kinase family phosphorylates the parkinson’s disease kinase LRRK2 at Ser935 and Ser910 during toll-like receptor signaling, PLoS One, 7, e39132, 10.1371/journal.pone.0039132 · DOI
  18. Eberth, 2009, In vitro GEF and GAP assays, Current Protocols in Cell Biology / Editorial Board, Juan S Bonifacino [Et Al], 14, 10.1002/0471143030.cb1409s43 · DOI
  19. Farley, 2000, Widespread recombinase expression using FLPeR (flipper) mice, Genesis, 28, 106, 10.1002/1526-968X(200011/12)28:3/4<106::AID-GENE30>3.0.CO;2-T · DOI
  20. Farrer, 2007, Lrrk2 G2385R is an ancestral risk factor for parkinson's disease in asia, Parkinsonism & Related Disorders, 13, 89, 10.1016/j.parkreldis.2006.12.001 · DOI
  21. Fell, 2015, MLi-2, a potent, selective, and centrally active compound for exploring the therapeutic potential and safety of LRRK2 kinase inhibition, Journal of Pharmacology and Experimental Therapeutics, 355, 397, 10.1124/jpet.115.227587 · DOI
  22. Gardet, 2010, LRRK2 is involved in the IFN- response and host response to pathogens, The Journal of Immunology, 185, 5577, 10.4049/jimmunol.1000548 · DOI
  23. Gillardon, 2009, Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability - a point of convergence in parkinsonian neurodegeneration?, Journal of Neurochemistry, 110, 1514, 10.1111/j.1471-4159.2009.06235.x · DOI
  24. Gitler, 2008, The parkinson's disease protein -synuclein disrupts cellular rab homeostasis, Proceedings of the National Academy of Sciences of the United States of America, 105, 145, 10.1073/pnas.0710685105 · DOI
  25. Gloeckner, 2009, The parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro, Journal of Neurochemistry, 109, 959, 10.1111/j.1471-4159.2009.06024.x · DOI
  26. Guo, 2013, Intermediates in the guanine nucleotide exchange reaction of Rab8 protein catalyzed by guanine nucleotide exchange factors Rabin8 and GRAB, Journal of Biological Chemistry, 288, 32466, 10.1074/jbc.M113.498329 · DOI
  27. Herzig, 2011, LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice, Human Molecular Genetics, 20, 4209, 10.1093/hmg/ddr348 · DOI
  28. Hinkle, 2012, LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors, Molecular Neurodegeneration, 7, 25, 10.1186/1750-1326-7-25 · DOI
  29. Hubner, 2010, Quantitative proteomics combined with BAC TransgeneOmics reveals in vivo protein interactions, The Journal of Cell Biology, 189, 739, 10.1083/jcb.200911091 · DOI · Paper page
  30. Humphrey, 2015, High-throughput phosphoproteomics reveals in vivo insulin signaling dynamics, Nature Biotechnology, 33, 990, 10.1038/nbt.3327 · DOI
  31. Hutagalung, 2011, Role of rab GTPases in membrane traffic and cell physiology, Physiological Reviews, 91, 119, 10.1152/physrev.00059.2009 · DOI · Paper page
  32. Imai, 2008, Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in drosophila, The EMBO Journal, 27, 2432, 10.1038/emboj.2008.163 · DOI
  33. Jaleel, 2007, LRRK2 phosphorylates moesin at threonine-558: characterization of how parkinson's disease mutants affect kinase activity, Biochemical Journal, 405, 307, 10.1042/BJ20070209 · DOI · Paper page
  34. Kanao, 2010, Activation of FoxO by LRRK2 induces expression of proapoptotic proteins and alters survival of postmitotic dopaminergic neuron in drosophila, Human Molecular Genetics, 19, 3747, 10.1093/hmg/ddq289 · DOI
  35. Kawakami, 2012, LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth, PLoS ONE, 7, e30834, 10.1371/journal.pone.0030834 · DOI
  36. Khan, 2005, Mutations in the gene LRRK2 encoding dardarin (pARK8) cause familial parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data, Brain, 128, 2786, 10.1093/brain/awh667 · DOI
  37. Krumova, 2015, Chemical genetic approach identifies microtubule affinity-regulating kinase 1 as a leucine-rich repeat kinase 2 substrate, The FASEB Journal, 29, 2980, 10.1096/fj.14-262329 · DOI
  38. Kumar, 2010, The parkinson's disease associated LRRK2 exhibits weaker in vitro phosphorylation of 4E-BP compared to autophosphorylation, PLoS One, 5, e8730, 10.1371/journal.pone.0008730 · DOI
  39. Lai, 2015, Phosphoproteomic screening identifies rab GTPases as novel downstream targets of PINK1, The EMBO Journal, 34, 2840, 10.15252/embj.201591593 · DOI
  40. Lees, 2009, Parkinson's disease, The Lancet, 373, 2055, 10.1016/S0140-6736(09)60492-X · DOI · Paper page
  41. Lemeer, 2009, The phosphoproteomics data explosion, Current Opinion in Chemical Biology, 13, 414, 10.1016/j.cbpa.2009.06.022 · DOI
  42. Liu, 2011, Inhibitors of LRRK2 kinase attenuate neurodegeneration and parkinson-like phenotypes in caenorhabditis elegans and drosophila parkinson's disease models, Human Molecular Genetics, 20, 3933, 10.1093/hmg/ddr312 · DOI
  43. MacLeod, 2013, RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and parkinson’s disease risk, Neuron, 77, 425, 10.1016/j.neuron.2012.11.033 · DOI · Paper page
  44. Mallick, 2010, Proteomics: a pragmatic perspective, Nature Biotechnology, 28, 695, 10.1038/nbt.1658 · DOI
  45. Martin, 2014, LRRK2 pathobiology in parkinson's disease, Journal of Neurochemistry, 131, 554, 10.1111/jnc.12949 · DOI
  46. Martin, 2014, Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in parkinson’s disease, Cell, 157, 472, 10.1016/j.cell.2014.01.064 · DOI · Paper page
  47. Mata, 2015, The RAB39B p.G192R mutation causes x-linked dominant parkinson’s disease, Molecular Neurodegeneration, 10, 50, 10.1186/s13024-015-0045-4 · DOI
  48. Matta, 2012, LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis, Neuron, 75, 1008, 10.1016/j.neuron.2012.08.022 · DOI · Paper page
  49. Nichols, 2009, Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in parkinson's disease, Biochemical Journal, 424, 47, 10.1042/BJ20091035 · DOI
  50. Nichols, 2010, 14-3-3 binding to LRRK2 is disrupted by multiple parkinson's disease-associated mutations and regulates cytoplasmic localization, Biochemical Journal, 430, 393, 10.1042/BJ20100483 · DOI
  51. Ohta, 2011, LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: impairment of the kinase activity by parkinson's disease-associated mutations, FEBS Letters, 585, 2165, 10.1016/j.febslet.2011.05.044 · DOI
  52. Olsen, 2006, Global, in vivo, and site-specific phosphorylation dynamics in signaling networks, Cell, 127, 635, 10.1016/j.cell.2006.09.026 · DOI
  53. Ong, 2002, Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics, Molecular & Cellular Proteomics, 1, 376, 10.1074/mcp.M200025-MCP200 · DOI · Paper page
  54. Papkovskaia, 2012, G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization, Human Molecular Genetics, 21, 4201, 10.1093/hmg/dds244 · DOI
  55. Pfeffer, 2005, Structural clues to rab GTPase functional diversity, Journal of Biological Chemistry, 280, 15485, 10.1074/jbc.R500003200 · DOI
  56. Pylypenko, 2003, Structure of rab escort protein-1 in complex with rab geranylgeranyltransferase, Molecular Cell, 11, 483, 10.1016/S1097-2765(03)00044-3 · DOI
  57. Qing, 2009, Lrrk2 phosphorylates alpha synuclein at serine 129: parkinson disease implications, Biochemical and Biophysical Research Communications, 387, 149, 10.1016/j.bbrc.2009.06.142 · DOI
  58. Rak, 2003, Structure of rab GDP-dissociation inhibitor in complex with prenylated YPT1 GTPase, Science, 302, 646, 10.1126/science.1087761 · DOI
  59. Reith, 2012, GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-n-arylbenzamide LRRK2 kinase inhibitor, Bioorganic & Medicinal Chemistry Letters, 22, 5625, 10.1016/j.bmcl.2012.06.104 · DOI
  60. Rivero-Ríos, 2015, Alterations in late endocytic trafficking related to the pathobiology of LRRK2-linked parkinson's disease, Biochemical Society Transactions, 43, 390, 10.1042/BST20140301 · DOI
  61. Roux, 2013, The coming of age of phosphoproteomics—from large data sets to inference of protein functions, Molecular & Cellular Proteomics, 12, 3453, 10.1074/mcp.R113.032862 · DOI
  62. Rudenko, 2014, Heterogeneity of leucine-rich repeat kinase 2 mutations: genetics, mechanisms and therapeutic implications, Neurotherapeutics, 11, 738, 10.1007/s13311-014-0284-z · DOI
  63. Satake, 2009, Genome-wide association study identifies common variants at four loci as genetic risk factors for parkinson's disease, Nature Genetics, 41, 1303, 10.1038/ng.485 · DOI
  64. Schapansky, 2014, Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy, Human Molecular Genetics, 23, 4201, 10.1093/hmg/ddu138 · DOI · Paper page
  65. Schapansky, 2015, The complex relationships between microglia, alpha-synuclein, and LRRK2 in parkinson’s disease, Neuroscience, 302, 74, 10.1016/j.neuroscience.2014.09.049 · DOI · Paper page
  66. Seabra, 2004, Controlling the location and activation of rab GTPases, Current Opinion in Cell Biology, 16, 451, 10.1016/j.ceb.2004.06.014 · DOI
  67. Sharma, 2014, Ultradeep human phosphoproteome reveals a distinct regulatory nature of tyr and Ser/Thr-based signaling, Cell Reports, 8, 1583, 10.1016/j.celrep.2014.07.036 · DOI
  68. Sheng, 2012, Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations, Science Translational Medicine, 4, 164ra161, 10.1126/scitranslmed.3004485 · DOI
  69. Simón-Sánchez, 2009, Genome-wide association study reveals genetic risk underlying parkinson's disease, Nature Genetics, 41, 1308, 10.1038/ng.487 · DOI · Paper page
  70. Taymans, 2015, Deregulation of protein translation control, a potential game-changing hypothesis for parkinson's disease pathogenesis, Trends in Molecular Medicine, 21, 466, 10.1016/j.molmed.2015.05.004 · DOI · Paper page
  71. Vizcaíno, 2014, ProteomeXchange provides globally coordinated proteomics data submission and dissemination, Nature Biotechnology, 32, 223, 10.1038/nbt.2839 · DOI
  72. West, 2005, From the cover: parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity, Proceedings of the National Academy of Sciences of the United States of America, 102, 16842, 10.1073/pnas.0507360102 · DOI · Paper page
  73. Westlake, 2011, Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (tRAPPII) complex-dependent trafficking of Rabin8 to the centrosome, Proceedings of the National Academy of Sciences of the United States of America, 108, 2759, 10.1073/pnas.1018823108 · DOI
  74. Wiggin, 2002, MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts, Molecular and Cellular Biology, 22, 2871, 10.1128/MCB.22.8.2871-2881.2002 · DOI
  75. Wilson, 2014, Mutations in RAB39B cause x-linked intellectual disability and early-onset parkinson disease with α-synuclein pathology, The American Journal of Human Genetics, 95, 729, 10.1016/j.ajhg.2014.10.015 · DOI
  76. Xiong, 2012, ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2, Journal of Neuroscience, 32, 3877, 10.1523/JNEUROSCI.4566-11.2012 · DOI
  77. Yao, 2013, Kinase inhibitors arrest neurodegeneration in cell and c. elegans models of LRRK2 toxicity, Human Molecular Genetics, 22, 328, 10.1093/hmg/dds431 · DOI
  78. Yun, 2015, An early endosome regulator, Rab5b, is an LRRK2 kinase substrate, Journal of Biochemistry, 157, 485, 10.1093/jb/mvv005 · DOI
  79. Yun, 2013, LRRK2 phosphorylates snapin and inhibits interaction of snapin with SNAP-25, Experimental & Molecular Medicine, 45, e36, 10.1038/emm.2013.68 · DOI
  80. Zhang, 2015, Commensal bacteria direct selective cargo sorting to promote symbiosis, Nature Immunology, 16, 918, 10.1038/ni.3233 · DOI · Paper page

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Metadata

Authors
Steger, M., Tonelli, F., Ito, G., Davies, P., Trost, M., Vetter, M., Wachter, S., Lorentzen, E., Duddy, G., Wilson, S., Baptista, M. A., Fiske, B. K., Fell, M. J., Morrow, J. A., Reith, A. D., Alessi, D. R., & Mann, M.
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2016-01-29
Volume
5
ISSN
2050-084X
DOI
10.7554/elife.12813
PMC
PMC4769169
Cited by
1,042
References
4
Language
en
Licence
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (P2ZHP3_151580)
  • Michael J. Fox Foundation for Parkinson's Research (6986)
  • Max-Planck-Gesellschaft
  • Medical Research Council (MC_UU_12016/3)

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