Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

Nature Communications

Volumn 5, Issue , 2014, Pages

  Godena, Vinay K ^a   Brookes Hocking, Nicholas ^b   Moller, Annekathrin ^c   Shaw, Gary ^c   Oswald, Matthew ^a,d   Sancho, Rosa M ^b,e   Miller, Christopher C J ^b   Whitworth, Alexander J ^a   De Vos, Kurt J ^a,c  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b KING'S COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF SHEFFIELD   (United Kingdom)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^e Alzheimer's Research UK   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TUBULIN; HISTONE DEACETYLASE 6; LEUCINE RICH REPEAT KINASE 2; SIRTUIN 2; TRICHOSTATIN A; DROSOPHILA PROTEIN; LRRK2 PROTEIN, DROSOPHILA; LRRK2 PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE;

ACETYLENE; DISEASE PREVALENCE; ENZYME ACTIVITY; MUTATION; NEUROLOGY; PATHOGENICITY; PROTEIN;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL STRUCTURE; CONTROLLED STUDY; GENE MUTATION; GENE SILENCING; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; IN VITRO STUDY; IN VIVO STUDY; LOCOMOTION; MICROTUBULE; MOTOR DYSFUNCTION; NERVE FIBER TRANSPORT; NONHUMAN; PARKINSON DISEASE; PROTEIN ACETYLATION; RAT; RNA INTERFERENCE; ROC COR DOMAIN MUTATION; TRANSGENIC DROSOPHILA; ACETYLATION; ANIMAL; AXON; CELL MOTION; CHEMISTRY; DROSOPHILA; ENZYMOLOGY; GENETICS; METABOLISM; MUTATION; NERVE CELL; PATHOPHYSIOLOGY; PROTEIN TERTIARY STRUCTURE; TRANSPORT AT THE CELLULAR LEVEL;

ACETYLATION; ANIMALS; AXONS; BIOLOGICAL TRANSPORT; CELL MOVEMENT; DROSOPHILA; DROSOPHILA PROTEINS; HUMANS; MICROTUBULES; MUTATION; NEURONS; PARKINSON DISEASE; PROTEIN STRUCTURE, TERTIARY; PROTEIN-SERINE-THREONINE KINASES; RATS;

EID: 84920426451     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms6245     Document Type: Article

References (68)

1. Paisan-Ruiz, C. et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44, 595-600 (2004).
2. Zimprich, A. et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601-607 (2004).
3. Gilks, W. P. et al. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 365, 415-416 (2005).
4. Satake, W. et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat. Genet. 41, 1303-1307 (2009).
5. Simon-Sanchez, J. et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat. Genet. 41, 1308-1312 (2009).
6. Guo, L. et al. 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 (2007).
7. Lewis, P. A. et al. The R1441C mutation of LRRK2 disrupts GTP hydrolysis. Biochem. Biophys. Res. Commun. 357, 668-671 (2007).
8. Greggio, E. et al. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol. Dis. 23, 329-341 (2006).
9. Jaleel, M. et al. LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity. Biochem. J. 405, 307-317 (2007).
10. Cookson, M. R. Cellular effects of LRRK2 mutations. Biochem. Soc. Trans. 40, 1070-1073 (2012).
11. MacLeod, D. et al. The familial Parkinsonism gene LRRK2 regulates neurite process morphology. Neuron 52, 587-593 (2006).
12. Parisiadou, L. et al. Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesis. J. Neurosci. 29, 13971-13980 (2009).
13. Plowey, E. D., Cherra, 3rd S. J., Liu, Y. J. & Chu, C. T. Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. J. Neurochem. 105, 1048-1056 (2008).
14. Gillardon, F. Interaction of elongation factor 1-alpha with leucine-rich repeat kinase 2 impairs kinase activity and microtubule bundling in vitro. Neuroscience 163, 533-539 (2009).
15. Gillardon, F. 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 (2009).
16. Caesar, M. et al. Leucine-rich repeat kinase 2 functionally interacts with microtubules and kinase-dependently modulates cell migration. Neurobiol. Dis. 54, 280-288 (2013).
17. Kett, L. R. et al. LRRK2 Parkinson disease mutations enhance its microtubule association. Hum. Mol. Genet. 21, 890-899 (2012).
18. Law, B. M. et al. A direct interaction between leucine-rich repeat kinase 2 and specific beta-tubulin isoforms regulates tubulin acetylation. J. Biol. Chem. 289, 895-908 (2014).
19. De Vos, K. J., Grierson, A. J., Ackerley, S. & Miller, C. C. J. Role of axonal transport in neurodegenerative diseases. Annu. Rev. Neurosci. 31, 151-173 (2008).
20. Liu, S. et al. Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet. 8, e1002537 (2012).
21. Saha, A. R. et al. Parkinson's disease alpha-synuclein mutations exhibit defective axonal transport in cultured neurons. J. Cell Sci. 117, 1017-1024 (2004).
22. Chu, Y. et al. Alterations in axonal transport motor proteins in sporadic and experimental Parkinson's disease. Brain 135, 2058-2073 (2012).
23. Wang, X. et al. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147, 893-906 (2011).
24. Weihofen, A., Thomas, K. J., Ostaszewski, B., Cookson, M. & Selkoe, D. J. Pink1 forms a multi-protein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking. Biochemistry 48, 2045-2052 (2009).
25. Reed, N. A. et al. Microtubule acetylation promotes kinesin-1 binding and transport. Curr. Biol. 16, 2166-2172 (2006).
26. Dompierre, J. P. et al. Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation. J. Neurosci. 27, 3571-3583 (2007).
27. Alegre-Abarrategui, J. et al. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum. Mol. Genet. 18, 4022-4034 (2009).
28. Hubbert, C. et al. HDAC6 is a microtubule-associated deacetylase. Nature 417, 455-458 (2002).
29. Southwood, C. M., Peppi, M., Dryden, S., Tainsky, M. A. & Gow, A. Microtubule deacetylases, SirT2 and HDAC6, in the nervous system. Neurochem. Res. 32, 187-195 (2007).
30. Haggarty, S. J., Koeller, K. M., Wong, J. C., Grozinger, C. M. & Schreiber, S. L. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc. Natl Acad. Sci. USA 100, 4389-4394 (2003).
31. Butler, K. V. et al. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J. Am. Chem. Soc. 132, 10842-10846 (2010).
32. Hu, E. et al. Identification of novel isoform-selective inhibitors within class I histone deacetylases. J. Pharmacol. Exp. Ther. 307, 720-728 (2003).
33. Outeiro, T. F. et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science 317, 516-519 (2007).
34. Shida, T., Cueva, J. G., Xu, Z., Goodman, M. B. & Nachury, M. V. The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation. Proc. Natl Acad. Sci. USA 107, 21517-21522 (2010).
35. Akella, J. S. et al. MEC-17 is an alpha-tubulin acetyltransferase. Nature 467, 218-222 (2010).
36. Kalebic, N. et al. Tubulin acetyltransferase alphaTAT1 destabilizes microtubules independently of its acetylation activity. Mol. Cell. Biol. 33, 1114-1123 (2013).
37. Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-608 (1998).
38. Valente, E. M. et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304, 1158-1160 (2004).
39. Cai, Q., Zakaria, H. M., Simone, A. & Sheng, Z. H. Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons. Curr. Biol. 22, 545-552 (2012).
40. Cartelli, D. et al. Microtubule dysfunction precedes transport impairment and mitochondria damage in MPP-induced neurodegeneration. J. Neurochem. 115, 247-258 (2010).
41. Morfini, G. et al. 1-Methyl-4-phenylpyridinium affects fast axonal transport by activation of caspase and protein kinase C. Proc. Natl Acad. Sci. USA 104, 2442-2447 (2007).
42. Kim-Han, J. S., Antenor-Dorsey, J. A. & O'Malley, K. L. The parkinsonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine axons. J. Neurosci. 31, 7212-7221 (2011).
43. Li, X. et al. 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 (2007).
44. Daniels, V. et al. Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant. J. Neurochem. 116, 304-315 (2011).
45. West, A. B. et al. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum. Mol. Genet. 16, 223-232 (2007).
46. West, A. B. et al. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Natl Acad. Sci. USA 102, 16842-16847 (2005).
47. Taymans, J. M. The GTPase function of LRRK2. Biochem. Soc. Trans. 40, 1063-1069 (2012).
48. Dzamko, N. et al. 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, 405-413 (2010).
49. Chen, S., Owens, G. C., Makarenkova, H. & Edelman, D. B. HDAC6 Regulates mitochondrial transport in hippocampal neurons. PLoS ONE 5, e10848 (2010).
50. d'Ydewalle, C., Bogaert, E. & Van Den Bosch, L. HDAC6 at the intersection of neuroprotection and neurodegeneration. Traffic 13, 771-779 (2012).
51. Kim, C. et al. HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons. PLoS ONE 7, e42983 (2012).
52. Govindarajan, N. et al. Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer's disease. EMBO Mol. Med. 5, 52-63 (2013).
53. Simoes-Pires, C. et al. HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs? Mol. Neurodegener. 8, 7 (2013).
54. Taes, I. et al. Hdac6 deletion delays disease progression in the SOD1G93A mouse model of ALS. Hum. Mol. Genet. 22, 1783-1790 (2013).
55. d'Ydewalle, C. et al. HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease. Nat. Med. 17, 968-974 (2011).
56. Ackerley, S. et al. Neurofilament heavy chain side-arm phosphorylation regulates axonal transport of neurofilaments. J. Cell Biol. 161, 489-495 (2003).
57. De Vos, K. J. et al. Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum. Mol. Genet. 16, 2720-2728 (2007).
58. Morotz, G. M. et al. Amyotrophic lateral sclerosis-associated mutant VAPBP56S perturbs calcium homeostasis to disrupt axonal transport of mitochondria. Hum. Mol. Genet. 21, 1979-1988 (2012).
59. De Vos, K. J. & Sheetz, M. P. Visualization and quantification of mitochondrial dynamics in living animal cells. Methods Cell Biol. 80, 627-682 (2007).
60. De Vos, K. J., Allan, V. J., Grierson, A. J. & Sheetz, M. P. Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission. Curr. Biol. 15, 678-683 (2005).
61. Liu, Z. et al. A Drosophila model for LRRK2-linked parkinsonism. Proc. Natl Acad. Sci. USA 105, 2693-2698 (2008).
62. Lin, C. H., Tsai, P. I., Wu, R. M. & Chien, C. T. LRRK2 G2019S mutation induces dendrite degeneration through mislocalization and phosphorylation of tau by recruiting autoactivated GSK3beta. J. Neurosci. 30, 13138-13149 (2010).
63. Imai, Y. et al. Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. EMBO J. 27, 2432-2443 (2008).
64. Lee, S. B., Kim, W., Lee, S. & Chung, J. Loss of LRRK2/PARK8 induces degeneration of dopaminergic neurons in Drosophila. Biochem. Biophys. Res. Commun. 358, 534-539 (2007).
65. Dietzl, G. et al. A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448, 151-156 (2007).
66. Greene, J. C. et al. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc. Natl Acad. Sci. USA 100, 4078-4083 (2003).
67. Kuznicki, M. L. & Gunawardena, S. In vivo visualization of synaptic vesicles within Drosophila larval segmental axons. J. Vis. Exp. 44, 2151 doi:10.3791/2151 (2010).
68. Meulener, M. et al. Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease. Curr. Biol. 15, 1572-1577 (2005).