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Regulation of vesicular trafficking by Parkinson's disease-associated genes

Department of Research for Parkinson's Disease, Juntendo University Graduate School of Medicine, Tokyo, Japan

Special Issues: Cell Signalling and Neuronal Cell Death

The regulatory mechanisms that control intracellular vesicular trafficking play important roles in cellular function and viability. Neurons have specific vesicular trafficking systems for synaptic vesicle formation, release and recycling. Synaptic vesicular trafficking impairments induce neuronal dysfunction and physiological and behavioral disorders. Parkinson's disease (PD) is an age-dependent neurodegenerative disorder characterized by dopamine depletion and loss of dopamine neurons in the midbrain. The molecular mechanism responsible for the neurodegeneration that occurs during PD is still not understood; however, recent functional analyses of familial PD causative genes suggest that a number of PD causative genes regulate intracellular vesicular trafficking, including synaptic vesicular dynamics. This review focuses on recent insights regarding the functions of PD causative genes, their relationship with vesicular trafficking and how mutations associated with PD affect vesicular dynamics and neuronal survival.
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Keywords Parkinson's disease; vesicular trafficking; synaptic vesicle dynamics; endosome; exocytosis; endocytosis; retromer; neurodegeneration

Citation: Tsuyoshi Inoshita, Yuzuru Imai. Regulation of vesicular trafficking by Parkinson's disease-associated genes. AIMS Molecular Science, 2015, 2(4): 461-475. doi: 10.3934/molsci.2015.4.461

References

  • 1. Sudhof TC (2004) The synaptic vesicle cycle. Annu Rev Neurosci 27: 509-547.    
  • 2. Schweizer FE, Ryan TA (2006) The synaptic vesicle: cycle of exocytosis and endocytosis. Curr Opin Neurobiol 16: 298-304.    
  • 3. Dittman J, Ryan TA (2009) Molecular circuitry of endocytosis at nerve terminals. Annu Rev Cell Dev Biol 25: 133-160.    
  • 4. Kuromi H, Kidokoro Y (1998) Two distinct pools of synaptic vesicles in single presynaptic boutons in a temperature-sensitive Drosophila mutant, shibire. Neuron 20: 917-925.    
  • 5. Richards DA, Guatimosim C, Betz WJ (2000) Two endocytic recycling routes selectively fill two vesicle pools in frog motor nerve terminals. Neuron 27: 551-559.    
  • 6. Mohrmann R, de Wit H, Connell E, et al. (2013) Synaptotagmin interaction with SNAP-25 governs vesicle docking, priming, and fusion triggering. J Neurosci 33: 14417-14430.    
  • 7. Verstreken P, Ly CV, Venken KJT, et al. (2005) Synaptic Mitochondria Are Critical for Mobilization of Reserve Pool Vesicles at Drosophila Neuromuscular Junctions. Neuron 47: 365-378.    
  • 8. Pelassa I, Zhao C, Pasche M, et al. (2014) Synaptic vesicles are . Front Mol Neurosci 7: 91-.    
  • 9. Benmerah A, Bayrou M, Cerf-Bensussan N, et al. (1999) Inhibition of clathrin-coated pit assembly by an Eps15 mutant. J Cell Sci 112 (Pt 9): 1303-1311.
  • 10. Watanabe S, Trimbuch T, Camacho-Perez M, et al. (2014) Clathrin regenerates synaptic vesicles from endosomes. Nature 515: 228-233.    
  • 11. Shimizu H, Kawamura S, Ozaki K (2003) An essential role of Rab5 in uniformity of synaptic vesicle size. J Cell Sci 116: 3583-3590.    
  • 12. Satoh AK, O'Tousa JE, Ozaki K, et al. (2005) Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors. Development 132: 1487-1497.    
  • 13. Stenmark H (2009) Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 10: 513-525.    
  • 14. Polymeropoulos MH, Lavedan C, Leroy E, et al. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276: 2045-2047.    
  • 15. Kruger R, Kuhn W, Muller T, et al. (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 18: 106-108.    
  • 16. Jakes R, Spillantini MG, Goedert M (1994) Identification of two distinct synucleins from human brain. FEBS Lett 345: 27-32.    
  • 17. Iwai A, Masliah E, Yoshimoto M, et al. (1995) The precursor protein of non-Aβ component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system. Neuron 14: 467-475.    
  • 18. Singleton AB, Farrer M, Johnson J, et al. (2003) alpha-Synuclein locus triplication causes Parkinson's disease. Science 302: 841.    
  • 19. Jao CC, Der-Sarkissian A, Chen J, et al. (2004) Structure of membrane-bound alpha-synuclein studied by site-directed spin labeling. Proc Natl Acad Sci U S A 101: 8331-8336.    
  • 20. Abd-Elhadi S, Honig A, Simhi-Haham D, et al. (2015) Total and Proteinase K-Resistant alpha-Synuclein Levels in Erythrocytes, Determined by their Ability to Bind Phospholipids, Associate with Parkinson's Disease. Sci Rep 5: 11120.    
  • 21. Cooper AA, Gitler AD, Cashikar A, et al. (2006) Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313: 324-328.    
  • 22. Feany MB, Bender WW (2000) A Drosophila model of Parkinson's disease. Nature 404: 394-398.    
  • 23. Periquet M, Fulga T, Myllykangas L, et al. (2007) Aggregated alpha-synuclein mediates dopaminergic neurotoxicity in vivo. J Neurosci 27: 3338-3346.    
  • 24. Chu Y, Morfini GA, Langhamer LB, et al. (2012) Alterations in axonal transport motor proteins in sporadic and experimental Parkinson's disease. Brain 135: 2058-2073.    
  • 25. Bayer TA, Jakala P, Hartmann T, et al. (1999) Neural expression profile of alpha-synuclein in developing human cortex. Neuroreport 10: 2799-2803.    
  • 26. Abeliovich A, Schmitz Y, Farinas I, et al. (2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25: 239-252.    
  • 27. Cabin DE, Shimazu K, Murphy D, et al. (2002) Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci 22: 8797-8807.
  • 28. Busch DJ, Oliphint PA, Walsh RB, et al. (2014) Acute increase of alpha-synuclein inhibits synaptic vesicle recycling evoked during intense stimulation. Mol Biol Cell 25: 3926-3941.    
  • 29. Wang L, Das U, Scott DA, et al. (2014) alpha-synuclein multimers cluster synaptic vesicles and attenuate recycling. Curr Biol 24: 2319-2326.    
  • 30. Breda C, Nugent ML, Estranero JG, et al. (2015) Rab11 modulates alpha-synuclein-mediated defects in synaptic transmission and behaviour. Hum Mol Genet 24: 1077-1091.    
  • 31. Paisan-Ruiz C, Jain S, Evans EW, et al. (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44: 595-600.    
  • 32. Zimprich A, Biskup S, Leitner P, et al. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44: 601-607.    
  • 33. Nuytemans K, Theuns J, Cruts M, et al. (2010) Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum Mutat 31: 763-780.    
  • 34. Simon-Sanchez J, Schulte C, Bras JM, et al. (2009) Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat Genet 41: 1308-1312.    
  • 35. Satake W, Nakabayashi Y, Mizuta I, et al. (2009) Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat Genet 41: 1303-1307.    
  • 36. Yao C, Johnson WM, Gao Y, et al. (2013) Kinase inhibitors arrest neurodegeneration in cell and C elegans models of LRRK2 toxicity. Hum Mol Genet 22: 328-344.    
  • 37. West AB, Moore DJ, Choi C, et al. (2007) Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum Mol Genet 16: 223-232.
  • 38. Smith WW, Pei Z, Jiang H, et al. (2005) Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci U S A 102: 18676-18681.    
  • 39. Tong Y, Pisani A, Martella G, et al. (2009) R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc Natl Acad Sci U S A 106: 14622-14627.    
  • 40. Imai Y, Gehrke S, Wang HQ, et al. (2008) Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. EMBO J 27: 2432-2443.    
  • 41. Imai Y, Kobayashi Y, Inoshita T, et al. (2015) The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway. PLoS Genet 11: e1005503.    
  • 42. Rivero-Rios P, Gomez-Suaga P, Fernandez B, et al. (2015) Alterations in late endocytic trafficking related to the pathobiology of LRRK2-linked Parkinson's disease. Biochem Soc Trans 43: 390-395.    
  • 43. Lee S, Liu HP, Lin WY, et al. (2010) LRRK2 Kinase Regulates Synaptic Morphology through Distinct Substrates at the Presynaptic and Postsynaptic Compartments of the Drosophila Neuromuscular Junction. J Neurosci 30: 16959-16969.    
  • 44. Matta S, Van Kolen K, da Cunha R, et al. (2012) LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis. Neuron 75: 1008-1021.    
  • 45. Arranz AM, Delbroek L, Van Kolen K, et al. (2015) LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism. J Cell Sci 128: 541-552.    
  • 46. Piccoli G, Condliffe SB, Bauer M, et al. (2011) LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. J Neurosci 31: 2225-2237.    
  • 47. Yun HJ, Park J, Ho DH, et al. (2013) LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25. Exp Mol Med 45: e36.    
  • 48. Shin N, Jeong H, Kwon J, et al. (2008) LRRK2 regulates synaptic vesicle endocytosis. Exp Cell Res 314: 2055-2065.    
  • 49. Yun HJ, Kim H, Ga I, et al. (2015) An early endosome regulator, Rab5b, is an LRRK2 kinase substrate. J Biochem 157: 485-495.    
  • 50. Kessels MM, Qualmann B (2002) Syndapins integrate N-WASP in receptor-mediated endocytosis. EMBO J 21: 6083-6094.    
  • 51. Kim Y, Kim S, Lee S, et al. (2005) Interaction of SPIN90 with dynamin I and its participation in synaptic vesicle endocytosis. J Neurosci 25: 9515-9523.    
  • 52. Soulet F, Yarar D, Leonard M, et al. (2005) SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Mol Biol Cell 16: 2058-2067.    
  • 53. Dodson MW, Zhang T, Jiang C, et al. (2012) Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning. Hum Mol Genet 21: 1350-1363.    
  • 54. Dodson MW, Leung LK, Lone M, et al. (2014) Novel ethyl methanesulfonate (EMS)-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo. Dis Model Mech 7: 1351-1363.    
  • 55. Esteves AR, M GF, Santos D, et al. (2015) The Upshot of LRRK2 Inhibition to Parkinson's Disease Paradigm. Mol Neurobiol 52: 1804-1820.    
  • 56. Gomez-Suaga P, Rivero-Rios P, Fdez E, et al. (2014) LRRK2 delays degradative receptor trafficking by impeding late endosomal budding through decreasing Rab7 activity. Hum Mol Genet 23: 6779-6796.    
  • 57. Tong Y, Yamaguchi H, Giaime E, et al. (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: 9879-9884.    
  • 58. Alegre-Abarrategui J, Christian H, Lufino MM, et al. (2009) LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet 18: 4022-4034.    
  • 59. Tong Y, Giaime E, Yamaguchi H, et al. (2012) Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway. Mol Neurodegener 7: 2.    
  • 60. Vilarino-Guell C, Wider C, Ross OA, et al. (2011) VPS35 mutations in Parkinson disease. Am J Hum Genet 89: 162-167.    
  • 61. Zimprich A, Benet-Pages A, Struhal W, et al. (2011) A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet 89: 168-175.    
  • 62. Nothwehr SF, Bruinsma P, Strawn LA (1999) Distinct domains within Vps35p mediate the retrieval of two different cargo proteins from the yeast prevacuolar/endosomal compartment. Mol Biol Cell 10: 875-890.    
  • 63. Korolchuk VI, Schutz MM, Gomez-Llorente C, et al. (2007) Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation. J Cell Sci 120: 4367-4376.    
  • 64. Kumar KR, Weissbach A, Heldmann M, et al. (2012) Frequency of the D620N Mutation in VPS35 in Parkinson Disease. Arch Neurol 69: 1360-1364.    
  • 65. Ando M, Funayama M, Li Y, et al. (2012) VPS35 mutation in Japanese patients with typical Parkinson's disease. Mov Disord 27: 1413-1417.    
  • 66. Follett J, Norwood SJ, Hamilton NA, et al. (2014) The Vps35 D620N mutation linked to Parkinson's disease disrupts the cargo sorting function of retromer. Traffic 15: 230-244.    
  • 67. Zavodszky E, Seaman MN, Moreau K, et al. (2014) Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy. Nat Commun 5: 3828-.    
  • 68. McGough IJ, Steinberg F, Jia D, et al. (2014) Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation. Curr Biol 24: 1670-1676.    
  • 69. Temkin P, Lauffer B, Jager S, et al. (2011) SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors. Nat Cell Biol 13: 715-721.    
  • 70. Zech T, Calaminus SD, Caswell P, et al. (2011) The Arp2/3 activator WASH regulates alpha5beta1-integrin-mediated invasive migration. J Cell Sci 124: 3753-3759.    
  • 71. Vilarino-Guell C, Rajput A, Milnerwood AJ, et al. (2014) DNAJC13 mutations in Parkinson disease. Hum Mol Genet 23: 1794-1801.    
  • 72. Popoff V, Mardones GA, Bai SK, et al. (2009) Analysis of Articulation Between Clathrin and Retromer in Retrograde Sorting on Early Endosomes. Traffic 10: 1868-1880.    
  • 73. Freeman CL, Hesketh G, Seaman MNJ (2014) RME-8 coordinates the activity of the WASH complex with the function of the retromer SNX dimer to control endosomal tubulation. J Cell Sci 127: 2053-2070.    
  • 74. Munsie LN, Milnerwood AJ, Seibler P, et al. (2015) Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson's disease VPS35 mutation p.D620N. Hum Mol Genet 24: 1691-1703.    
  • 75. Wang HS, Toh J, Ho P, et al. (2014) In vivo evidence of pathogenicity of VPS35 mutations in the Drosophila. Mol Brain 7: 73.    
  • 76. Wen L, Tang FL, Hong Y, et al. (2011) VPS35 haploinsufficiency increases Alzheimer's disease neuropathology. J Cell Biol 195: 765-779.    
  • 77. MacLeod DA, Rhinn H, Kuwahara T, et al. (2013) RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. Neuron 77: 425-439.    
  • 78. Beilina A, Rudenko IN, Kaganovich A, et al. (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: 2626-2631.    
  • 79. Linhart R, Wong SA, Cao J, et al. (2014) Vacuolar protein sorting 35 (Vps35) rescues locomotor deficits and shortened lifespan in Drosophila expressing a Parkinson's disease mutant of Leucine-Rich Repeat Kinase 2 (LRRK2). Mol Neurodegener 9: 23.    
  • 80. Edvardson S, Cinnamon Y, Ta-Shma A, et al. (2012) A deleterious mutation in DNAJC6 encoding the neuronal-specific clathrin-uncoating co-chaperone auxilin, is associated with juvenile parkinsonism. PLoS One 7: e36458.    
  • 81. Koroglu C, Baysal L, Cetinkaya M, et al. (2013) DNAJC6 is responsible for juvenile parkinsonism with phenotypic variability. Parkinsonism Relat Disord 19: 320-324.    
  • 82. Fotin A, Cheng YF, Sliz P, et al. (2004) Molecular model for a complete clathrin lattice from electron cryomicroscopy. Nature 432: 573-579.    
  • 83. Young JC, Barral JM, Hartl FU (2003) More than folding: localized functions of cytosolic chaperones. Trends Biochem Sci 28: 541-547.    
  • 84. Pankratz N, Wilk JB, Latourelle JC, et al. (2009) Genomewide association study for susceptibility genes contributing to familial Parkinson disease. Hum Genet 124: 593-605.    
  • 85. Yim YI, Sun T, Wu LG, et al. (2010) Endocytosis and clathrin-uncoating defects at synapses of auxilin knockout mice. Proc Natl Acad Sci U S A 107: 4412-4417.    
  • 86. Dumitriu A, Pacheco CD, Wilk JB, et al. (2011) Cyclin-G-associated kinase modifies alpha-synuclein expression levels and toxicity in Parkinson's disease: results from the GenePD Study. Hum Mol Genet 20: 1478-1487.    
  • 87. Krebs CE, Karkheiran S, Powell JC, et al. (2013) The Sac1 domain of SYNJ1 identified mutated in a family with early-onset progressive Parkinsonism with generalized seizures. Hum Mutat 34: 1200-1207.    
  • 88. Nalls MA, Pankratz N, Lill CM, et al. (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat Genet 46: 989-993.    
  • 89. Luo WJ, Chang A (1997) Novel genes involved in endosomal traffic in yeast revealed by suppression of a targeting-defective plasma membrane ATPase mutant. Mol Biol Cell 8: 1779-1779.
  • 90. Verstreken P, Koh TW, Schulze KL, et al. (2003) Synaptojanin is recruited by Endophilin to promote synaptic vesicle uncoating. Neuron 40: 733-748.    
  • 91. Harris TW, Hartwieg E, Horvitz HR, et al. (2000) Mutations in synaptojanin disrupt synaptic vesicle recycling. J Cell Biol 150: 589-599.    
  • 92. Schuske KR, Richmond JE, Matthies DS, et al. (2003) Endophilin is required for synaptic vesicle endocytosis by localizing synaptojanin. Neuron 40: 749-762.    
  • 93. Periquet M, Corti O, Jacquier S, et al. (2005) Proteomic analysis of parkin knockout mice: alterations in energy metabolism, protein handling and synaptic function. J Neurochem 95: 1259-1276.    
  • 94. Kitada T, Pisani A, Porter DR, et al. (2007) Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc Natl Acad Sci U S A 104: 11441-11446.    
  • 95. Morais VA, Verstreken P, Roethig A, et al. (2009) Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function. EMBO Mol Med 1: 99-111.    
  • 96. Vincent A, Briggs L, Chatwin GF, et al. (2012) parkin-induced defects in neurophysiology and locomotion are generated by metabolic dysfunction and not oxidative stress. Hum Mol Genet 21: 1760-1769.    
  • 97. Shiba-Fukushima K, Inoshita T, Hattori N, et al. (2014) PINK1-Mediated Phosphorylation of Parkin Boosts Parkin Activity in Drosophila. PLoS Genet 10: e1004391.    
  • 98. Braschi E, Goyon V, Zunino R, et al. (2010) Vps35 Mediates Vesicle Transport between the Mitochondria and Peroxisomes. Curr Biol 20: 1310-1315.    
  • 99. Tang FL, Liu W, Hu JX, et al. (2015) VPS35 Deficiency or Mutation Causes Dopaminergic Neuronal Loss by Impairing Mitochondrial Fusion and Function. Cell Rep 12: 1631-1643.    
  • 100. Cali T, Ottolini D, Negro A, et al. (2012) alpha-Synuclein Controls Mitochondrial Calcium Homeostasis by Enhancing Endoplasmic Reticulum-Mitochondria Interactions. J Biol Chem 287: 17914-17929.    
  • 101. Nakamura K, Nemani VM, Azarbal F, et al. (2011) Direct Membrane Association Drives Mitochondrial Fission by the Parkinson Disease-associated Protein alpha-Synuclein. J Biol Chem 286: 20710-20726.    
  • 102. Wong YC, Holzbaur EL (2014) Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci U S A 42: E4439-48.    
  • 103. Guardia-Laguarta C, Area-Gomez E, Rub C, et al. (2014) alpha-Synuclein Is Localized to Mitochondria-Associated ER Membranes. J Neurosci 34: 249-259.    

 

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