In vivo evidence of pathogenicity of VPS35 mutations in the Drosophila
Tóm tắt
Mutations of VPS35, a component of the retromer complex have been associated with late onset familial Parkinson's disease. The D620N mutation in VPS35 appears to be most prevalent, however, P316S was found in two cases within the same family and a control, whereas L774M was identified in 6 cases and 1 control. In vivo evidence of their pathogenicity is lacking. Here we investigated the in vivo effects of P316S, D620N and L774M using Drosophila as a model. We generated transgenic human VPS35-expressing mutations and demonstrated that VPS35 D620N transgenic flies led to late-onset loss of TH-positive DA neurons, poor mobility, shortened lifespans and increased sensitivity to rotenone, a PD-linked environmental toxin, with some of these phenotypes observed for P316S but not in L774M transgenic flies. We conclude that D620N and to a smaller extent P316S are associated with pathogenicity in PD.
Tài liệu tham khảo
Tan EK, Skipper LM: Pathogenic mutations in Parkinson disease. Hum Mutat. 2007, 28 (7): 641-653. 10.1002/humu.20507.
Skinner C, Seaman M, Skinner C, Seaman M: The role of retromer in neurodegenerative disease. Research and Perspectives in Alzheimer's Disease. Edited by: St. George-Hyslop PH, Mobley WCC, Yves C. 2009, Springer Berlin, Heidelberg, 125-140.
Bonifacino JS, Hurley JH: Retromer. Curr Opin Cell Biol. 2008, 20 (4): 427-436. 10.1016/j.ceb.2008.03.009.
Zimprich A, Benet-Pagès A, Struhal W, Graf E, Eck SH, Offman MN, Haubenberger D, Spielberger S, Schulte EC, Lichtner P, Rossle SC, Klopp N, Wolf E, Seppi K, Pirker W, Presslauer S, Mollenhauer B, Katzenschlager R, Foki T, Hotzy C, Reinthaler E, Harutyunyan A, Kralovics R, Peters A, Zimprich F, Brücke T, Poewe W, Auff E, Trenkwalder C, Rost B, et al: A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet. 2011, 89 (1): 168-175. 10.1016/j.ajhg.2011.06.008.
Vilariño-Güell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, Soto-Ortolaza AI, Cobb SA, Wilhoite GJ, Bacon JA, Behrouz B, Melrose HL, Hentati E, Puschmann A, Evans DM, Conibear E, Wasserman WW, Aasly JO, Burkhard PR, Djaldetti R, Ghika J, Hentati F, Krygowska-Wajs A, Lynch T, Melamed E, Rajput A, Rajput AH, Solida A, Wu RM, Uitti RJ, et al: VPS35 mutations in Parkinson disease. Am J Hum Genet. 2011, 89 (1): 162-167. 10.1016/j.ajhg.2011.06.001.
Ando M, Funayama M, Li Y, Kashihara K, Murakami Y, Ishizu N, Toyoda C, Noguchi K, Hashimoto T, Nakano N, Sasaki R, Kokubo Y, Kuzuhara S, Ogaki K, Yamashita C, Yoshino H, Hatano T, Tomiyama H, Hattori N: VPS35 mutation in Japanese patients with typical Parkinson's disease. Mov Disord. 2012, 27 (11): 1413-1417. 10.1002/mds.25145.
Guo JF, Sun QY, Lv ZY, Yu RL, Li K, Zhang YH, Tian JY, Xia K, Yan XX, Tang BS: VPS35 gene variants are not associated with Parkinson's disease in the mainland Chinese population. Parkinsonism Relat Disord. 2012, 18 (8): 983-985. 10.1016/j.parkreldis.2012.05.002.
Lesage S, Condroyer C, Klebe S, Honoré A, Tison F, Brefel-Courbon C, Dürr A, Brice A: Identification of VPS35 mutations replicated in French families with Parkinson disease. Neurology. 2012, 78 (18): 1449-1450. 10.1212/WNL.0b013e318253d5f2.
Sheerin UM, Charlesworth G, Bras J, Guerreiro R, Bhatia K, Foltynie T, Limousin P, Silveira-Moriyama L, Lees A, Wood N: Screening for VPS35 mutations in Parkinson's disease.Neurobiol Aging 2012, 33(4):838. e1-838.e5.,
Sharma M, Ioannidis JPA, Aasly JO, Annesi G, Brice A, Bertram L, Bozi M, Barcikowska M, Crosiers D, Clarke CE, Facheris MF, Farrer M, Garraux G, Gispert S, Auburger G, Vilariño-Güell C, Hadjigeorgiou GM, Hicks AA, Hattori N, Jeon BS, Jamrozik Z, Krygowska-Wajs A, Lesage S, Lill CM, Lin JJ, Lynch T, Lichtner P, Lang AE, Libioulle C, Murata M, et al: A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants. J Med Genet. 2012, 49 (11): 721-726. 10.1136/jmedgenet-2012-101155.
Korolchuk VI, Schütz MM, Gómez-Llorente C, Rocha J, Lansu NR, Collins SM, Wairkar YP, Robinson IM, OóKane CJ: Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation. J Cell Sci. 2007, 120 (24): 4367-4376. 10.1242/jcs.012336.
Dong B, Kakihara K, Otani T, Wada H, Hayashi S: Rab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control.Nat Commun 2013, 4:1358.,
MacLeod DA, Rhinn H, Kuwahara T, Zolin A, Di Paolo G, McCabe BD, MacCabe BD, Marder KS, Honig LS, Clark LN, Small SA, Abeliovich A: RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. Neuron. 2013, 77 (3): 425-439. 10.1016/j.neuron.2012.11.033.
Whitworth AJ, Theodore DA, Greene JC, Beneš H, Wes PD, Pallanck LJ: Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease. Proc Natl Acad Sci. 2005, 102 (22): 8024-8029. 10.1073/pnas.0501078102.
Wang C, Lu R, Ouyang X, Ho MWL, Chia W, Yu F, Lim KL: Drosophila overexpressing parkin R275W mutant exhibits dopaminergic neuron degeneration and mitochondrial abnormalities. J Neurosci. 2007, 27 (32): 8563-8857. 10.1523/JNEUROSCI.0218-07.2007.
Ng CH, Mok SZS, Koh C, Ouyang X, Fivaz ML, Tan EK, Dawson VL, Dawson TM, Yu F, Lim KL: Parkin protects against LRRK2 G2019S mutant-induced dopaminergic neurodegeneration in Drosophila. J Neurosci. 2009, 29 (36): 11257-11262. 10.1523/JNEUROSCI.2375-09.2009.
Hierro A, Rojas AL, Rojas R, Murthy N, Effantin G, Kajava AV, Steven AC, Bonifacino JS, Hurley JH: Functional architecture of the retromer cargo-recognition complex. Nature. 2007, 449 (7165): 1063-1067. 10.1038/nature06216.
Collins BM, Skinner CF, Watson PJ, Seaman MNJ, Owen DJ: Vps29 has a phosphoesterase fold that acts as a protein interaction scaffold for retromer assembly. Nat Struct Mol Biol. 2005, 12 (7): 594-602. 10.1038/nsmb954.
Collins BM: The structure and function of the retromer protein complex. Traffic. 2008, 9 (11): 1811-1822. 10.1111/j.1600-0854.2008.00777.x.
Zavodszky E, Seaman MN, Moreau K, Jimenez-Sanchez M, Breusegem SY, Harbour ME, Rubinsztein DC: Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy.Nat Commun 2014, 5:3828.,
Follett J, Norwood SJ, Hamilton NA, Mohan M, Kovtun O, Tay S, Zhe Y, Wood SA, Mellick GD, Silburn PA, Collins BM, Bugarcic A, Teasdale RD: The Vps35 D620N mutation linked to Parkinson's disease disrupts the cargo sorting function of retromer. Traffic. 2014, 15 (2): 230-244. 10.1111/tra.12136.
Tsika E, Glauser L, Moser R, Fiser A, Daniel G, Sheerin UM, Lees A, Troncoso JC, Lewis PA, Bandopadhyay R, Schneider BL, Moore DJ: Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration. Hum Mol Genet. 2014, 23 (17): 4621-4638. 10.1093/hmg/ddu178.
Braschi E, Goyon V, Zunino R, Mohanty A, Xu L, McBride HM: Vps35 mediates vesicle transport between the mitochondria and peroxisomes. Curr Biol. 2010, 20 (14): 1310-1315. 10.1016/j.cub.2010.05.066.
Bi F, Li F, Huang C, Zhou H: Pathogenic mutation in VPS35 impairs its protection against MPP(+) cytotoxicity. Int J Biol Sci. 2013, 9 (2): 149-155. 10.7150/ijbs.5617.