Lipid rafts involvement in the pathogenesis of parkinson's disease

Frontiers in Bioscience - Landmark

Volumn 20, Issue 2, 2015, Pages 263-279

  Kubo, Shin Ichiro ^a   Hatanos, Taku ^a   Hattori, Nobutaka ^a  

^a JUNTENDO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Alpha Synuclein; Lipid rafts; LRRK2; Parkin; Parkinson's disease; Review

Indexed keywords

CELL MEMBRANE; GENETICS; HUMAN; PARKINSON DISEASE; PATHOPHYSIOLOGY; PHYSIOLOGY;

HUMANS; MEMBRANE MICRODOMAINS; PARKINSON DISEASE;

EID: 84919708862     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/4308     Document Type: Review

References (127)

1. Ari Helenius, Werner Kuhlbrandt, Dieter Osterhelt, Kai Simons. The lipid bilayer. In: Molecular Biology of THE CELL, Chap 10 Membrane structure. Eds: B Alberts, A Johnson, J Lewis, M Raff, K Roberts, P Walter New York, New York and Abingdon, Oxfordshire (2008)
2. Simons, K., E. Ikonen. Functional rafts in cell membranes. Nature 387, 569-572 (1997) DOI: 10.1038/42408
3. Gomez-Mouton, C., R. A. Lacalle, E. Mira, S. Jimenez-Baranda, D. F. Barber, A. C. Carrera, A. C. Martinez, S. Manes. Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. J Cell Biol 164, 759-768 (2004) DOI: 10.1083/jcb.200309101
4. Scheiffele, P., A. Rietveld, T. Wilk, K. Simons. Influenza viruses select ordered lipid domains during budding from the plasma membrane. J Biol Chem 274, 2038-2044 (1999) DOI: 10.1074/jbc.274.4.2038
5. Schengrund, C. L. Lipid rafts: keys to neurodegeneration. Brain Res Bull 82, 7-17 (2010) DOI: 10.1016/j.brainresbull.2010.02.013
6. Marin, R., J. A. Rojo, N. Fabelo, C. E. Fernandez, M. Diaz. Lipid raft disarrangement as a result of neuropathological progresses: a novel strategy for early diagnosis? Neuroscience 245, 26-39 (2013) DOI: 10.1016/j.neuroscience.2013.04.025
7. Simons, K., D. Toomre. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1, 31-39 (2000) DOI: 10.1038/35036052
8. Brown, R. E. Sphingolipid organization in biomembranes: what physical studies of model membranes reveal. J Cell Sci 111 (Pt 1), 1-9 (1998)
9. Shaikh, S. R., M. R. Brzustowicz, N. Gustafson, W. Stillwell, S. R. Wassall. Monounsaturated PE does not phase-separate from the lipid raft molecules sphingomyelin and cholesterol: role for polyunsaturation? Biochemistry 41, 10593-10602 (2002) DOI: 10.1021/bi025712b
10. Shaikh, S. R., V. Cherezov, M. Caffrey, W. Stillwell, S. R. Wassall. Interaction of cholesterol with a docosahexaenoic acid-containing phosphatidylethanolamine: trigger for microdomain/raft formation? Biochemistry 42, 12028-12037 (2003) DOI: 10.1021/bi034931+
11. Sharma, P., R. Varma, R. C. Sarasij, Ira, K. Gousset, G. Krishnamoorthy, M. Rao, S. Mayor. Nanoscale organization of multiple GPI-anchored proteins in living cell membranes. Cell 116, 577-589 (2004) DOI: 10.1016/S0092-8674(04)00167-9
12. Lenne, P. F., L. Wawrezinieck, F. Conchonaud, O. Wurtz, A. Boned, X. J. Guo, H. Rigneault, H. T. He, D. Marguet. Dynamic molecular confinement in the plasma membrane by microdomains and the cytoskeleton meshwork. EMBO J 25, 3245-3256 (2006) DOI: 10.1038/sj.emboj.7601214
13. Vyas, N., D. Goswami, A. Manonmani, P. Sharma, H. A. Ranganath, K. VijayRaghavan, L. S. Shashidhara, R. Sowdhamini, S. Mayor. Nanoscale organization of hedgehog is essential for long-range signaling. Cell 133, 1214-1227 (2008) DOI: 10.1016/j.cell.2008.05.026
14. Pinaud, F., X. Michalet, G. Iyer, E. Margeat, H. P. Moore, S. Weiss. Dynamic partitioning of a glycosyl-phosphatidylinositol-anchored protein in glycosphingolipid-rich microdomains imaged by single-quantum dot tracking. Traffic 10, 691-712 (2009) DOI: 10.1111/j.1600-0854.2009.00902.x
15. Schermelleh, L., R. Heintzmann, H. Leonhardt. A guide to super-resolution fluorescence microscopy. J Cell Biol 190, 165-175 (2010) DOI: 10.1083/jcb.201002018
16. Hell, S. W. Far-field optical nanoscopy. Science 316, 1153-1158 (2007) DOI: 10.1126/science.1137395
17. Shroff, H., C. G. Galbraith, J. A. Galbraith, E. Betzig. Live-cell photoactivated localization microscopy of nanoscale adhesion dynamics. Nat Methods 5, 417-423 (2008) DOI: 10.1038/nmeth.1202
18. Rust, M. J., M. Bates, X. Zhuang. Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat Methods 3, 793-795 (2006) DOI: 10.1038/nmeth929
19. Suzuki, K. G., T. K. Fujiwara, M. Edidin, A. Kusumi. Dynamic recruitment of phospholipase C gamma at transiently immobilized GPI-anchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking study 2. J Cell Biol 177, 731-742 (2007) DOI: 10.1083/jcb.200609175
20. Suzuki, K. G., T. K. Fujiwara, F. Sanematsu, R. Iino, M. Edidin, A. Kusumi. GPI-anchored receptor clusters transiently recruit Lyn and G alpha for temporary cluster immobilization and Lyn activation: single-molecule tracking study 1. J Cell Biol 177, 717-730 (2007) DOI: 10.1083/jcb.200609174
21. Stefanova, I., V. Horejsi, I. J. Ansotegui, W. Knapp, H. Stockinger. GPI-anchored cell-surface molecules complexed to protein tyrosine kinases. Science 254, 1016-1019 (1991) DOI: 10.1126/science.1719635
22. Seminario, M. C., S. C. Bunnell. Signal initiation in T-cell receptor microclusters. Immunol Rev 221, 90-106 (2008) DOI: 10.1111/j.1600-065X.2008.00593.x
23. Sonnino, S., A. Prinetti. Membrane domains and the "lipid raft" concept. Curr Med Chem 20, 4-21 (2013)
24. Paratcha, G., C. F. Ibanez. Lipid rafts and the control of neurotrophic factor signaling in the nervous system: variations on a theme. Curr Opin Neurobiol 12, 542-549 (2002) DOI: 10.1016/S0959-4388(02)00363-X
25. Tsui-Pierchala, B. A., M. Encinas, J. Milbrandt, E. M. Johnson, Jr. Lipid rafts in neuronal signaling and function. Trends Neurosci 25, 412-417 (2002) DOI: 10.1016/S0166-2236(02)02215-4
26. Nagappan, G., B. Lu. Activity-dependent modulation of the BDNF receptor TrkB: mechanisms and implications. Trends Neurosci 28, 464-471 (2005) DOI: 10.1016/j.tins.2005.07.003
27. Decker, L., W. Baron, C. Ffrench-Constant. Lipid rafts: microenvironments for integrin-growth factor interactions in neural development. Biochem Soc Trans 32, 426-430 (2004) DOI: 10.1042/BST0320426
28. Santuccione, A., V. Sytnyk, I. Leshchyns'ka, M. Schachner. Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. J Cell Biol 169, 341-354 (2005) DOI: 10.1083/jcb.200409127
29. Ichikawa, N., K. Iwabuchi, H. Kurihara, K. Ishii, T. Kobayashi, T. Sasaki, N. Hattori, Y. Mizuno, K. Hozumi, Y. Yamada, E. Arikawa-Hirasawa. Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is crucial for neurite outgrowth. J Cell Sci 122, 289-299 (2009) DOI: 10.1242/jcs.030338
30. Tooze, S. A., G. J. Martens, W. B. Huttner. Secretory granule biogenesis: rafting to the SNARE. Trends Cell Biol 11, 116-122 (2001) DOI: 10.1016/S0962-8924(00)01907-3
31. McKerracher, L. Ganglioside rafts as MAG receptors that mediate blockade of axon growth. Proc Natl Acad Sci U S A 99, 7811-7813 (2002) DOI: 10.1073/pnas.132280299
32. Vyas, A. A., H. V. Patel, S. E. Fromholt, M. Heffer-Lauc, K. A. Vyas, J. Dang, M. Schachner, R. L. Schnaar. Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration. Proc Natl Acad Sci U S A 99, 8412-8417 (2002) DOI: 10.1073/pnas.072211699
33. Boggs, J. M., H. Wang, W. Gao, D. N. Arvanitis, Y. Gong, W. Min. A glycosynapse in myelin? Glycoconj J 21, 97-110 (2004) DOI: 10.1023/B:GLYC.0000044842.34958.f8
34. Castillon, G. A., R. Watanabe, M. Taylor, T. M. Schwabe, H. Riezman. Concentration of GPI-anchored proteins upon ER exit in yeast. Traffic 10, 186-200 (2009) DOI: 10.1111/j.1600-0854.2008.00857.x
35. Fujita, M., M. Umemura, T. Yoko-o, Y. Jigami. PER1 is required for GPI-phospholipase A2 activity and involved in lipid remodeling of GPI-anchored proteins. Mol Biol Cell 17, 5253-5264 (2006) DOI: 10.1091/mbc.E06-08-0715
36. Fujita, M., O. T. Yoko, Y. Jigami. Inositol deacylation by Bst1p is required for the quality control of glycosylphosphatidylinositol-anchored proteins. Mol Biol Cell 17, 834-850 (2006) DOI: 10.1091/mbc.E05-05-0443
37. Schuck, S., K. Simons. Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane. J Cell Sci 117, 5955-5964 (2004) DOI: 10.1242/jcs.01596
38. Head, B. P., H. H. Patel, P. A. Insel. Interaction of membrane/lipid rafts with the cytoskeleton: Impact on signaling and function: Membrane/lipid rafts, mediators of cytoskeletal arrangement and cell signaling. Biochim Biophys Acta, (2013)
39. Bekris, L. M., I. F. Mata, C. P. Zabetian. The genetics of Parkinson disease. J Geriatr Psychiatry Neurol 23, 228-242 (2010) DOI: 10.1177/0891988710383572
40. Braak, H., K. Del Tredici, U. Rub, R. A. de Vos, E. N. Jansen Steur, E. Braak. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24, 197-211 (2003) DOI: 10.1016/S0197-4580(02)00065-9
41. Schapira, A. H., J. M. Cooper, D. Dexter, J. B. Clark, P. Jenner, C. D. Marsden. Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem 54, 823-827 (1990) DOI: 10.1111/j.1471-4159.1990.tb02325.x
42. Hattori, N., M. Tanaka, T. Ozawa, Y. Mizuno. Immunohistochemical studies on complexes I, II, III, and IV of mitochondria in Parkinson's disease. Ann Neurol 30, 563-571 (1991) DOI: 10.1002/ana.410300409
43. Ben-Shachar, D., P. Riederer, M. B. Youdim. Iron-melanin interaction and lipid peroxidation: implications for Parkinson's disease. J Neurochem 57, 1609-1614 (1991) DOI: 10.1111/j.1471-4159.1991.tb06358.x
44. Jenner, P. Oxidative stress in Parkinson's disease. Ann Neurol 53 Suppl 3, S26-36; discussion S36-28 (2003)
45. Klein, C., M. G. Schlossmacher. The genetics of Parkinson disease: Implications for neurological care. Nat Clin Pract Neurol 2, 136-146 (2006) DOI: 10.1038/ncpneuro0126
46. Kubo, S., N. Hattori, Y. Mizuno. Recessive Parkinson's disease. Mov Disord 21, 885-893 (2006) DOI: 10.1002/mds.20841
47. Hatano, T., S. Kubo, S. Sato, N. Hattori. Pathogenesis of familial Parkinson's disease: new insights based on monogenic forms of Parkinson's disease. J Neurochem 111, 1075-1093 (2009) DOI: 10.1111/j.1471-4159.2009.06403.x
48. Clayton, D. F., J. M. George. Synucleins in synaptic plasticity and neurodegenerative disorders. J Neurosci Res 58, 120-129 (1999) DOI: 10.1002/(SICI)1097-4547(19991001)58:1〈120::AID-JNR12〉3.0.CO;2-E
49. Hashimoto, M., E. Masliah. Alpha-synuclein in Lewy body disease and Alzheimer's disease. Brain Pathol 9, 707-720 (1999) DOI: 10.1111/j.1750-3639.1999.tb00552.x
50. Kruger, R., T. Muller, O. Riess. Involvement of alpha-synuclein in Parkinson's disease and other neurodegenerative disorders. J Neural Transm 107, 31-40 (2000) DOI: 10.1007/s007020050002
51. Duda, J. E., V. M. Lee, J. Q. Trojanowski. Neuropathology of synuclein aggregates. J Neurosci Res 61, 121-127 (2000) DOI: 10.1002/1097-4547(20000715)61:2〈121::AID-JNR1〉3.0.CO;2-4
52. Polymeropoulos, M. H., C. Lavedan, E. Leroy, S. E. Ide, A. Dehejia, A. Dutra, B. Pike, H. Root, J. Rubenstein, R. Boyer, E. S. Stenroos, S. Chandrasekharappa, A. Athanassiadou, T. Papapetropoulos, W. G. Johnson, A. M. Lazzarini, R. C. Duvoisin, G. Di Iorio, L. I. Golbe, R. L. Nussbaum. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047 (1997) DOI: 10.1126/science.276.5321.2045
53. Kruger, R., W. Kuhn, T. Muller, D. Woitalla, M. Graeber, S. Kosel, H. Przuntek, J. T. Epplen, L. Schols, O. Riess. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 18, 106-108 (1998) DOI: 10.1038/ng0298-106
54. Zarranz, J. J., A. Fernandez-Bedoya, I. Lambarri, J. C. Gomez-Esteban, E. Lezcano, J. Zamacona, P. Madoz. Abnormal sleep architecture is an early feature in the E46K familial synucleinopathy. Mov Disord 20, 1310-1315 (2005) DOI: 10.1002/mds.20581
55. Singleton, A. B., M. Farrer, J. Johnson, A. Singleton, S. Hague, J. Kachergus, M. Hulihan, T. Peuralinna, A. Dutra, R. Nussbaum, S. Lincoln, A. Crawley, M. Hanson, D. Maraganore, C. Adler, M. R. Cookson, M. Muenter, M. Baptista, D. Miller, J. Blancato, J. Hardy, K. Gwinn-Hardy. alpha-Synuclein locus triplication causes Parkinson's disease. Science 302, 841 (2003) DOI: 10.1126/science.1090278
56. Ibanez, P., A. M. Bonnet, B. Debarges, E. Lohmann, F. Tison, P. Pollak, Y. Agid, A. Durr, A. Brice. Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease. Lancet 364, 1169-1171 (2004) DOI: 10.1016/S0140-6736(04)17104-3
57. Chartier-Harlin, M. C., J. Kachergus, C. Roumier, V. Mouroux, X. Douay, S. Lincoln, C. Levecque, L. Larvor, J. Andrieux, M. Hulihan, N. Waucquier, L. Defebvre, P. Amouyel, M. Farrer, A. Destee. Alphasynuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364, 1167-1169 (2004) DOI: 10.1016/S0140-6736(04)17103-1
58. Nishioka, K., S. Hayashi, M. J. Farrer, A. B. Singleton, H. Yoshino, H. Imai, T. Kitami, K. Sato, R. Kuroda, H. Tomiyama, K. Mizoguchi, M. Murata, T. Toda, I. Imoto, J. Inazawa, Y. Mizuno, N. Hattori. Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's disease. Ann Neurol 59, 298-309 (2006) DOI: 10.1002/ana.20753
59. Spillantini, M. G., M. L. Schmidt, V. M. Lee, J. Q. Trojanowski, R. Jakes, M. Goedert. Alpha-synuclein in Lewy bodies. Nature 388, 839-840 (1997) DOI: 10.1038/42166
60. Spillantini, M. G., R. A. Crowther, R. Jakes, M. Hasegawa, M. Goedert. alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc Natl Acad Sci U S A 95, 6469-6473 (1998) DOI: 10.1073/pnas.95.11.6469
61. Maroteaux, L., J. T. Campanelli, R. H. Scheller. Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8, 2804-2815 (1988)
62. Jakes, R., M. G. Spillantini, M. Goedert. Identification of two distinct synucleins from human brain. FEBS Lett 345, 27-32 (1994) DOI: 10.1016/0014-5793(94)00395-5
63. Iwai, A., E. Masliah, M. Yoshimoto, N. Ge, L. Flanagan, H. A. de Silva, A. Kittel, T. Saitoh. The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system. Neuron 14, 467-475 (1995) DOI: 10.1016/0896-6273(95)90302-X
64. Murphy, D. D., S. M. Rueter, J. Q. Trojanowski, V. M. Lee. Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J Neurosci 20, 3214-3220 (2000)
65. George, J. M., H. Jin, W. S. Woods, D. F. Clayton. Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron 15, 361-372 (1995) DOI: 10.1016/0896-6273(95)90040-3
66. Abeliovich, A., Y. Schmitz, I. Farinas, D. Choi-Lundberg, W. H. Ho, P. E. Castillo, N. Shinsky, J. M. Verdugo, M. Armanini, A. Ryan, M. Hynes, H. Phillips, D. Sulzer, A. Rosenthal. Mice lacking alphasynuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25, 239-252 (2000) DOI: 10.1016/S0896-6273(00)80886-7
67. Cabin, D. E., K. Shimazu, D. Murphy, N. B. Cole, W. Gottschalk, K. L. McIlwain, B. Orrison, A. Chen, C. E. Ellis, R. Paylor, B. Lu, R. L. Nussbaum. Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci 22, 8797-8807 (2002)
68. Nemani, V. M., W. Lu, V. Berge, K. Nakamura, B. Onoa, M. K. Lee, F. A. Chaudhry, R. A. Nicoll, R. H. Edwards. Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65, 66-79 (2010) DOI: 10.1016/j.neuron.2009.12.023
69. Ueda, K., H. Fukushima, E. Masliah, Y. Xia, A. Iwai, M. Yoshimoto, D. A. Otero, J. Kondo, Y. Ihara, T. Saitoh. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci U S A 90, 11282-11286 (1993) DOI: 10.1073/pnas.90.23.11282
70. Kahle, P. J., M. Neumann, L. Ozmen, V. Muller, H. Jacobsen, A. Schindzielorz, M. Okochi, U. Leimer, H. van Der Putten, A. Probst, E. Kremmer, H. A. Kretzschmar, C. Haass. Subcellular localization of wildtype and Parkinson's disease-associated mutant alpha-synuclein in human and transgenic mouse brain. J Neurosci 20, 6365-6373 (2000)
71. Davidson, W. S., A. Jonas, D. F. Clayton, J. M. George. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem 273, 9443-9449 (1998) DOI: 10.1074/jbc.273.16.9443
72. Eliezer, D., E. Kutluay, R. Bussell, Jr., G. Browne. Conformational properties of alpha-synuclein in its free and lipid-associated states. J Mol Biol 307, 1061-1073 (2001) DOI: 10.1006/jmbi.2001.4538
73. Chandra, S., X. Chen, J. Rizo, R. Jahn, T. C. Sudhof. A broken alpha-helix in folded alpha- Synuclein. J Biol Chem 278, 15313-15318 (2003) DOI: 10.1074/jbc.M213128200
74. Jensen, P. H., M. S. Nielsen, R. Jakes, C. G. Dotti, M. Goedert. Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson's disease mutation. J Biol Chem 273, 26292-26294 (1998) DOI: 10.1074/jbc.273.41.26292
75. Cole, N. B., D. D. Murphy, T. Grider, S. Rueter, D. Brasaemle, R. L. Nussbaum. Lipid droplet binding and oligomerization properties of the Parkinson's disease protein alpha-synuclein. J Biol Chem 277, 6344-6352 (2002) DOI: 10.1074/jbc.M108414200
76. Outeiro, T. F., S. Lindquist. Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science 302, 1772-1775 (2003) DOI: 10.1126/science.1090439
77. Fortin, D. L., M. D. Troyer, K. Nakamura, S. Kubo, M. D. Anthony, R. H. Edwards. Lipid rafts mediate the synaptic localization of alpha-synuclein. J Neurosci 24, 6715-6723 (2004) DOI: 10.1523/JNEUROSCI.1594-04.2004
78. Kubo, S., V. M. Nemani, R. J. Chalkley, M. D. Anthony, N. Hattori, Y. Mizuno, R. H. Edwards, D. L. Fortin. A combinatorial code for the interaction of alpha-synuclein with membranes. J Biol Chem 280, 31664-31672 (2005) DOI: 10.1074/jbc.M504894200
79. Mata, I. F., W. J. Wedemeyer, M. J. Farrer, J. P. Taylor, K. A. Gallo. LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci 29, 286-293 (2006) DOI: 10.1016/j.tins.2006.03.006
80. Marin, I., W. N. van Egmond, P. J. van Haastert. The Roco protein family: a functional perspective. FASEB J 22, 3103-3110 (2008) DOI: 10.1096/fj.08-111310
81. Biskup, S., D. J. Moore, F. Celsi, S. Higashi, A. B. West, S. A. Andrabi, K. Kurkinen, S. W. Yu, J. M. Savitt, H. J. Waldvogel, R. L. Faull, P. C. Emson, R. Torp, O. P. Ottersen, T. M. Dawson, V. L. Dawson. Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann Neurol 60, 557-569 (2006) DOI: 10.1002/ana.21019
82. Melrose, H., S. Lincoln, G. Tyndall, D. Dickson, M. Farrer. Anatomical localization of leucine-rich repeat kinase 2 in mouse brain. Neuroscience 139, 791-794 (2006) DOI: 10.1016/j.neuroscience.2006.01.017
83. Higashi, S., D. J. Moore, R. E. Colebrooke, S. Biskup, V. L. Dawson, H. Arai, T. M. Dawson, P. C. Emson. Expression and localization of Parkinson's disease-associated leucine-rich repeat kinase 2 in the mouse brain. J Neurochem 100, 368-381 (2007) DOI: 10.1111/j.1471-4159.2006.04246.x
84. Higashi, S., S. Biskup, A. B. West, D. Trinkaus, V. L. Dawson, R. L. Faull, H. J. Waldvogel, H. Arai, T. M. Dawson, D. J. Moore, P. C. Emson. Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain. Brain Res 1155, 208-219 (2007) DOI: 10.1016/j.brainres.2007.04.034
85. West, A. B., D. J. Moore, S. Biskup, A. Bugayenko, W. W. Smith, C. A. Ross, V. L. Dawson, T. M. Dawson. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A 102, 16842-16847 (2005) DOI: 10.1073/pnas.0507360102
86. Gloeckner, C. J., N. Kinkl, A. Schumacher, R. J. Braun, E. O'Neill, T. Meitinger, W. Kolch, H. Prokisch, M. Ueffing. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum Mol Genet 15, 223-232 (2006) DOI: 10.1093/hmg/ddi439
87. Hatano, T., S. Kubo, S. Imai, M. Maeda, K. Ishikawa, Y. Mizuno, N. Hattori. Leucine-rich repeat kinase 2 associates with lipid rafts. Hum Mol Genet 16, 678-690 (2007) DOI: 10.1093/hmg/ddm013
88. MacLeod, D., J. Dowman, R. Hammond, T. Leete, K. Inoue, A. Abeliovich. The familial Parkinsonism gene LRRK2 regulates neurite process morphology. Neuron 52, 587-593 (2006) DOI: 10.1016/j.neuron.2006.10.008
89. Shin, N., H. Jeong, J. Kwon, H. Y. Heo, J. J. Kwon, H. J. Yun, C. H. Kim, B. S. Han, Y. Tong, J. Shen, T. Hatano, N. Hattori, K. S. Kim, S. Chang, W. Seol. LRRK2 regulates synaptic vesicle endocytosis. Exp Cell Res 314, 2055-2065 (2008) DOI: 10.1016/j.yexcr.2008.02.015
90. Sakaguchi-Nakashima, A., J. Y. Meir, Y. Jin, K. Matsumoto, N. Hisamoto. LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins. Curr Biol 17, 592-598 (2007) DOI: 10.1016/j.cub.2007.01.074
91. Li, Y., W. Liu, T. F. Oo, L. Wang, Y. Tang, V. Jackson-Lewis, C. Zhou, K. Geghman, M. Bogdanov, S. Przedborski, M. F. Beal, R. E. Burke, C. Li. Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat Neurosci 12, 826-828 (2009) DOI: 10.1038/nn.2349
92. Jaleel, M., R. J. Nichols, M. Deak, D. G. Campbell, F. Gillardon, A. Knebel, D. R. Alessi. LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity. Biochem J 405, 307-317 (2007) DOI: 10.1042/BJ20070209
93. Gandhi, P. N., X. Wang, X. Zhu, S. G. Chen, A. L. Wilson-Delfosse. The Roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubules. J Neurosci Res 86, 1711-1720 (2008) DOI: 10.1002/jnr.21622
94. Dachsel, J. C., J. P. Taylor, S. S. Mok, O. A. Ross, K. M. Hinkle, R. M. Bailey, J. H. Hines, J. Szutu, B. Madden, L. Petrucelli, M. J. Farrer. Identification of potential protein interactors of Lrrk2. Parkinsonism Relat Disord 13, 382-385 (2007) DOI: 10.1016/j.parkreldis.2007.01.008
95. Shimura, H., N. Hattori, S. Kubo, Y. Mizuno, S. Asakawa, S. Minoshima, N. Shimizu, K. Iwai, T. Chiba, K. Tanaka, T. Suzuki. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25, 302-305 (2000) DOI: 10.1038/77060
96. Imai, Y., M. Soda, R. Takahashi. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem 275, 35661-35664 (2000) DOI: 10.1074/jbc.C000447200
97. Zhang, Y., J. Gao, K. K. Chung, H. Huang, V. L. Dawson, T. M. Dawson. Parkin functions as an E2- dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc Natl Acad Sci U S A 97, 13354-13359 (2000) DOI: 10.1073/pnas.240347797
98. Imai, Y., M. Soda, H. Inoue, N. Hattori, Y. Mizuno, R. Takahashi. An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105, 891-902 (2001) DOI: 10.1016/S0092-8674(01)00407-X
99. Sakata, E., Y. Yamaguchi, E. Kurimoto, J. Kikuchi, S. Yokoyama, S. Yamada, H. Kawahara, H. Yokosawa, N. Hattori, Y. Mizuno, K. Tanaka, K. Kato. Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain. EMBO Rep 4, 301-306 (2003) DOI: 10.1038/sj.embor.embor764
100. Hershko, A., A. Ciechanover. The ubiquitin system for protein degradation. Annu Rev Biochem 61, 761-807 (1992) DOI: 10.1146/annurev.bi.61.070192.003553
101. Doss-Pepe, E. W., L. Chen, K. Madura. Alpha-synuclein and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chains. J Biol Chem 280, 16619-16624 (2005) DOI: 10.1074/jbc.M413591200
102. Lim, K. L., K. C. Chew, J. M. Tan, C. Wang, K. K. Chung, Y. Zhang, Y. Tanaka, W. Smith, S. Engelender, C. A. Ross, V. L. Dawson, T. M. Dawson. Parkin mediates nonclassical, proteasomalindependent ubiquitination of synphilin-1: implications for Lewy body formation. J Neurosci 25, 2002-2009 (2005) DOI: 10.1523/JNEUROSCI.4474-04.2005
103. Haglund, K., S. Sigismund, S. Polo, I. Szymkiewicz, P. P. Di Fiore, I. Dikic. Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation. Nat Cell Biol 5, 461-466 (2003) DOI: 10.1038/ncb983
104. Nakatsu, F., M. Sakuma, Y. Matsuo, H. Arase, S. Yamasaki, N. Nakamura, T. Saito, H. Ohno. A Dileucine signal in the ubiquitin moiety. Possible involvement in ubiquitination-mediated endocytosis. J Biol Chem 275, 26213-26219 (2000) DOI: 10.1074/jbc.M907720199
105. Roth, A. F., N. G. Davis. Ubiquitination of the PEST-like endocytosis signal of the yeast a-factor receptor. J Biol Chem 275, 8143-8153 (2000) DOI: 10.1074/jbc.275.11.8143
106. Shih, S. C., K. E. Sloper-Mould, L. Hicke. Monoubiquitin carries a novel internalization signal that is appended to activated receptors. EMBO J 19, 187-198 (2000) DOI: 10.1093/emboj/19.2.187
107. Hicke, L. Ubiquitin-dependent internalization and down-regulation of plasma membrane proteins. FASEB J 11, 1215-1226 (1997)
108. Hicke, L. Protein regulation by monoubiquitin. Nat Rev Mol Cell Biol 2, 195-201 (2001) DOI: 10.1038/35056583
109. Katzmann, D. J., G. Odorizzi, S. D. Emr. Receptor downregulation and multivesicular-body sorting. Nat Rev Mol Cell Biol 3, 893-905 (2002) DOI: 10.1038/nrm973
110. Shimura, H., N. Hattori, S. Kubo, M. Yoshikawa, T. Kitada, H. Matsumine, S. Asakawa, S. Minoshima, Y. Yamamura, N. Shimizu, Y. Mizuno. Immunohistochemical and subcellular localization of Parkin protein: absence of protein in autosomal recessive juvenile parkinsonism patients. Ann Neurol 45, 668-672 (1999) DOI: 10.1002/1531-8249(199905)45:5〈668::AID-ANA19〉3.0.CO;2-Z
111. Kubo, S. I., T. Kitami, S. Noda, H. Shimura, Y. Uchiyama, S. Asakawa, S. Minoshima, N. Shimizu, Y. Mizuno, N. Hattori. Parkin is associated with cellular vesicles. J Neurochem 78, 42-54 (2001) DOI: 10.1046/j.1471-4159.2001.00364.x
112. Fallon, L., F. Moreau, B. G. Croft, N. Labib, W. J. Gu, E. A. Fon. Parkin and CASK/LIN-2 associate via a PDZ-mediated interaction and are co-localized in lipid rafts and postsynaptic densities in brain. J Biol Chem 277, 486-491 (2002) DOI: 10.1074/jbc.M109806200
113. Shendelman, S., A. Jonason, C. Martinat, T. Leete, A. Abeliovich. DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation. PLoS Biol 2, e362 (2004) DOI: 10.1371/journal.pbio.0020362
114. Canet-Aviles, R. M., M. A. Wilson, D. W. Miller, R. Ahmad, C. McLendon, S. Bandyopadhyay, M. J. Baptista, D. Ringe, G. A. Petsko, M. R. Cookson. The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci U S A 101, 9103-9108 (2004) DOI: 10.1073/pnas.0402959101
115. Takahashi, K., T. Taira, T. Niki, C. Seino, S. M. Iguchi-Ariga, H. Ariga. DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor. J Biol Chem 276, 37556-37563 (2001) DOI: 10.1074/jbc.M101730200
116. Taira, T., Y. Saito, T. Niki, S. M. Iguchi-Ariga, K. Takahashi, H. Ariga. DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5, 213-218 (2004) DOI: 10.1038/sj.embor.7400074
117. Inden, M., T. Taira, Y. Kitamura, T. Yanagida, D. Tsuchiya, K. Takata, D. Yanagisawa, K. Nishimura, T. Taniguchi, Y. Kiso, K. Yoshimoto, T. Agatsuma, S. Koide-Yoshida, S. M. Iguchi-Ariga, S. Shimohama, H. Ariga. PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model. Neurobiol Dis 24, 144-158 (2006) DOI: 10.1016/j.nbd.2006.06.004
118. Menzies, F. M., S. C. Yenisetti, K. T. Min. Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress. Curr Biol 15, 1578-1582 (2005) DOI: 10.1016/j.cub.2005.07.036
119. Meulener, M., A. J. Whitworth, C. E. Armstrong-Gold, P. Rizzu, P. Heutink, P. D. Wes, L. J. Pallanck, N. M. Bonini. Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease. Curr Biol 15, 1572-1577 (2005) DOI: 10.1016/j.cub.2005.07.064
120. Kim, R. H., P. D. Smith, H. Aleyasin, S. Hayley, M. P. Mount, S. Pownall, A. Wakeham, A. J. You- Ten, S. K. Kalia, P. Horne, D. Westaway, A. M. Lozano, H. Anisman, D. S. Park, T. W. Mak. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A 102, 5215-5220 (2005) DOI: 10.1073/pnas.0501282102
121. Goldberg, M. S., A. Pisani, M. Haburcak, T. A. Vortherms, T. Kitada, C. Costa, Y. Tong, G. Martella, A. Tscherter, A. Martins, G. Bernardi, B. L. Roth, E. N. Pothos, P. Calabresi, J. Shen. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45, 489-496 (2005) DOI: 10.1016/j.neuron.2005.01.041
122. Olzmann, J. A., J. R. Bordelon, E. C. Muly, H. D. Rees, A. I. Levey, L. Li, L. S. Chin. Selective enrichment of DJ-1 protein in primate striatal neuronal processes: implications for Parkinson's disease. J Comp Neurol 500, 585-599 (2007) DOI: 10.1002/cne.21191
123. Usami, Y., T. Hatano, S. Imai, S. Kubo, S. Sato, S. Saiki, Y. Fujioka, Y. Ohba, F. Sato, M. Funayama, H. Eguchi, K. Shiba, H. Ariga, J. Shen, N. Hattori. DJ-1 associates with synaptic membranes. Neurobiol Dis 43, 651-662 (2011) DOI: 10.1016/j.nbd.2011.05.014
124. Kim, K. S., J. S. Kim, J. Y. Park, Y. H. Suh, I. Jou, E. H. Joe, S. M. Park. DJ-1 Associates with lipid rafts by palmitoylation and regulates lipid rafts-dependent endocytosis in astrocytes. Hum Mol Genet, (2013) DOI: 10.1093/hmg/ddt332
125. den Jager, W. A. Sphingomyelin in Lewy inclusion bodies in Parkinson's disease. Arch Neurol 21, 615-619 (1969) DOI: 10.1001/archneur.1969.00480180071006
126. Gai, W. P., H. X. Yuan, X. Q. Li, J. T. Power, P. C. Blumbergs, P. H. Jensen. In situ and in vitro study of colocalization and segregation of alpha-synuclein, ubiquitin, and lipids in Lewy bodies. Exp Neurol 166, 324-333 (2000) DOI: 10.1006/exnr.2000.7527
127. Fabelo, N., V. Martin, G. Santpere, R. Marin, L. Torrent, I. Ferrer, M. Diaz. Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson's disease and incidental Parkinson's disease. Mol Med 17, 1107-1118 (2011) DOI: 10.2119/molmed.2011.00119