Skip to main content
Top
Published in: Molecular Brain 1/2011

Open Access 01-12-2011 | Research

Genome-wide screen for modifiers of Parkinson's disease genes in Drosophila

Authors: Caroline Fernandes, Yong Rao

Published in: Molecular Brain | Issue 1/2011

Login to get access

Abstract

Background

Mutations in parkin and PTEN-induced kinase 1 (Pink1) lead to autosomal recessive forms of Parkinson's disease (PD). parkin and Pink1 encode a ubiquitin-protein ligase and a mitochondrially localized serine/threonine kinase, respectively. Recent studies have implicated Parkin and Pink1 in a common and evolutionarily conserved pathway for protecting mitochondrial integrity.

Results

To systematically identify novel components of the PD pathways, we generated a genetic background that allowed us to perform a genome-wide F1 screen for modifiers of Drosophila parkin (park) and Pink1 mutant phenotype. From screening ~80% of the fly genome, we identified a number of cytological regions that interact with park and/or Pink1. Among them, four cytological regions were selected for identifying corresponding PD-interacting genes. By analyzing smaller deficiency chromosomes, available transgenic RNAi lines, and P-element insertions, we identified five PD-interacting genes. Among them, opa1 and drp1 have been previously implicated in the PD pathways, whereas debra (dbr), Pi3K21B and β4GalNAcTA are novel PD-interacting genes.

Conclusions

We took an unbiased genetic approach to systematically isolate modifiers of PD genes in Drosophila. Further study of novel PD-interacting genes will shed new light on the function of PD genes and help in the development of new therapeutic strategies for treating Parkinson's disease.
Appendix
Available only for authorised users
Literature
1.
go back to reference Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N: Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998, 392: 605-608. 10.1038/33416.CrossRefPubMed Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N: Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998, 392: 605-608. 10.1038/33416.CrossRefPubMed
2.
go back to reference Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW: Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004, 304: 1158-1160. 10.1126/science.1096284.CrossRefPubMed Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW: Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004, 304: 1158-1160. 10.1126/science.1096284.CrossRefPubMed
3.
go back to reference Valente EM, Salvi S, Ialongo T, Marongiu R, Elia AE, Caputo V, Romito L, Albanese A, Dallapiccola B, Bentivoglio AR: PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann Neurol. 2004, 56: 336-341. 10.1002/ana.20256.CrossRefPubMed Valente EM, Salvi S, Ialongo T, Marongiu R, Elia AE, Caputo V, Romito L, Albanese A, Dallapiccola B, Bentivoglio AR: PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann Neurol. 2004, 56: 336-341. 10.1002/ana.20256.CrossRefPubMed
4.
go back to reference Bertoli-Avella AM, Giroud-Benitez JL, Akyol A, Barbosa E, Schaap O, van der Linde HC, Martignoni E, Lopiano L, Lamberti P, Fincati E, Antonini A, Stocchi F, Montagna P, Squitieri F, Marini P, Abbruzzese G, Fabbrini G, Marconi R, Dalla Libera A, Trianni G, Guidi M, De Gaetano A, Boff Maegawa G, De Leo A, Gallai V, de Rosa G, Vanacore N, Meco G, van Duijn CM, Oostra BA, et al: Novel parkin mutations detected in patients with early-onset Parkinson's disease. Mov Disord. 2005, 20: 424-431. 10.1002/mds.20343.CrossRefPubMed Bertoli-Avella AM, Giroud-Benitez JL, Akyol A, Barbosa E, Schaap O, van der Linde HC, Martignoni E, Lopiano L, Lamberti P, Fincati E, Antonini A, Stocchi F, Montagna P, Squitieri F, Marini P, Abbruzzese G, Fabbrini G, Marconi R, Dalla Libera A, Trianni G, Guidi M, De Gaetano A, Boff Maegawa G, De Leo A, Gallai V, de Rosa G, Vanacore N, Meco G, van Duijn CM, Oostra BA, et al: Novel parkin mutations detected in patients with early-onset Parkinson's disease. Mov Disord. 2005, 20: 424-431. 10.1002/mds.20343.CrossRefPubMed
5.
go back to reference Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW, Agid Y, Brice A: Association between early-onset Parkinson's disease and mutations in the parkin gene. N Engl J Med. 2000, 342: 1560-1567. 10.1056/NEJM200005253422103.CrossRefPubMed Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW, Agid Y, Brice A: Association between early-onset Parkinson's disease and mutations in the parkin gene. N Engl J Med. 2000, 342: 1560-1567. 10.1056/NEJM200005253422103.CrossRefPubMed
6.
go back to reference Imai Y, Soda M, Takahashi R: Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem. 2000, 275: 35661-35664. 10.1074/jbc.C000447200.CrossRefPubMed Imai Y, Soda M, Takahashi R: Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem. 2000, 275: 35661-35664. 10.1074/jbc.C000447200.CrossRefPubMed
7.
go back to reference Zhang Y, Gao J, Chung KK, Huang H, Dawson VL, Dawson TM: 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 USA. 2000, 97: 13354-13359. 10.1073/pnas.240347797.CrossRefPubMed Zhang Y, Gao J, Chung KK, Huang H, Dawson VL, Dawson TM: 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 USA. 2000, 97: 13354-13359. 10.1073/pnas.240347797.CrossRefPubMed
8.
go back to reference Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R: An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell. 2001, 105: 891-902. 10.1016/S0092-8674(01)00407-X.CrossRefPubMed Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R: An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell. 2001, 105: 891-902. 10.1016/S0092-8674(01)00407-X.CrossRefPubMed
9.
go back to reference Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, Schneider R, Mizuno Y, Kosik KS, Selkoe DJ: Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science. 2001, 293: 263-269. 10.1126/science.1060627.CrossRefPubMed Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, Schneider R, Mizuno Y, Kosik KS, Selkoe DJ: Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science. 2001, 293: 263-269. 10.1126/science.1060627.CrossRefPubMed
10.
go back to reference Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM: Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. 2001, 7: 1144-1150. 10.1038/nm1001-1144.CrossRefPubMed Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM: Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. 2001, 7: 1144-1150. 10.1038/nm1001-1144.CrossRefPubMed
11.
go back to reference Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A: Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron. 2003, 37: 735-749. 10.1016/S0896-6273(03)00084-9.CrossRefPubMed Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A: Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron. 2003, 37: 735-749. 10.1016/S0896-6273(03)00084-9.CrossRefPubMed
12.
go back to reference Pridgeon JW, Olzmann JA, Chin LS, Li L: PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLoS Biol. 2007, 5: e172-10.1371/journal.pbio.0050172.PubMedCentralCrossRefPubMed Pridgeon JW, Olzmann JA, Chin LS, Li L: PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLoS Biol. 2007, 5: e172-10.1371/journal.pbio.0050172.PubMedCentralCrossRefPubMed
13.
go back to reference Plun-Favreau H, Klupsch K, Moisoi N, Gandhi S, Kjaer S, Frith D, Harvey K, Deas E, Harvey RJ, McDonald N, Wood NW, Martins LM, Downward J: The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. Nat Cell Biol. 2007, 9: 1243-1252. 10.1038/ncb1644.CrossRefPubMed Plun-Favreau H, Klupsch K, Moisoi N, Gandhi S, Kjaer S, Frith D, Harvey K, Deas E, Harvey RJ, McDonald N, Wood NW, Martins LM, Downward J: The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. Nat Cell Biol. 2007, 9: 1243-1252. 10.1038/ncb1644.CrossRefPubMed
14.
go back to reference Kim Y, Park J, Kim S, Song S, Kwon SK, Lee SH, Kitada T, Kim JM, Chung J: PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochem Biophys Res Commun. 2008, 377: 975-980. 10.1016/j.bbrc.2008.10.104.CrossRefPubMed Kim Y, Park J, Kim S, Song S, Kwon SK, Lee SH, Kitada T, Kim JM, Chung J: PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochem Biophys Res Commun. 2008, 377: 975-980. 10.1016/j.bbrc.2008.10.104.CrossRefPubMed
15.
go back to reference Guo M: What have we learned from Drosophila models of Parkinson's disease?. Prog Brain Res. 2010, 184: 3-16.PubMed Guo M: What have we learned from Drosophila models of Parkinson's disease?. Prog Brain Res. 2010, 184: 3-16.PubMed
16.
go back to reference Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ: The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci USA. 2008, 105: 1638-1643. 10.1073/pnas.0709336105.PubMedCentralCrossRefPubMed Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ: The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci USA. 2008, 105: 1638-1643. 10.1073/pnas.0709336105.PubMedCentralCrossRefPubMed
17.
go back to reference Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang JW, Yang L, Beal MF, Vogel H, Lu B: Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci USA. 2006, 103: 10793-10798. 10.1073/pnas.0602493103.PubMedCentralCrossRefPubMed Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang JW, Yang L, Beal MF, Vogel H, Lu B: Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci USA. 2006, 103: 10793-10798. 10.1073/pnas.0602493103.PubMedCentralCrossRefPubMed
18.
go back to reference Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J: Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006, 441: 1157-1161. 10.1038/nature04788.CrossRefPubMed Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J: Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006, 441: 1157-1161. 10.1038/nature04788.CrossRefPubMed
19.
go back to reference Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M: Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006, 441: 1162-1166. 10.1038/nature04779.CrossRefPubMed Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M: Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006, 441: 1162-1166. 10.1038/nature04779.CrossRefPubMed
20.
go back to reference Dagda RK, Chu CT: Mitochondrial quality control: insights on how Parkinson's disease related genes PINK1, parkin, and Omi/HtrA2 interact to maintain mitochondrial homeostasis. J Bioenerg Biomembr. 2009, 41: 473-479. 10.1007/s10863-009-9255-1.PubMedCentralCrossRefPubMed Dagda RK, Chu CT: Mitochondrial quality control: insights on how Parkinson's disease related genes PINK1, parkin, and Omi/HtrA2 interact to maintain mitochondrial homeostasis. J Bioenerg Biomembr. 2009, 41: 473-479. 10.1007/s10863-009-9255-1.PubMedCentralCrossRefPubMed
21.
go back to reference Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, Gispert S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Kruger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C: Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci. 2007, 27: 12413-12418. 10.1523/JNEUROSCI.0719-07.2007.CrossRefPubMed Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, Gispert S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Kruger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C: Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci. 2007, 27: 12413-12418. 10.1523/JNEUROSCI.0719-07.2007.CrossRefPubMed
22.
go back to reference Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magrane J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S: PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA. 2010, 107: 378-383. 10.1073/pnas.0911187107.PubMedCentralCrossRefPubMed Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magrane J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S: PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA. 2010, 107: 378-383. 10.1073/pnas.0911187107.PubMedCentralCrossRefPubMed
23.
go back to reference Ziviani E, Tao RN, Whitworth AJ: Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci USA. 2010, 107: 5018-5023. 10.1073/pnas.0913485107.PubMedCentralCrossRefPubMed Ziviani E, Tao RN, Whitworth AJ: Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci USA. 2010, 107: 5018-5023. 10.1073/pnas.0913485107.PubMedCentralCrossRefPubMed
24.
go back to reference Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W: PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010, 12: 119-131. 10.1038/ncb2012.CrossRefPubMed Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W: PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010, 12: 119-131. 10.1038/ncb2012.CrossRefPubMed
25.
go back to reference Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ: PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010, 8: e1000298-10.1371/journal.pbio.1000298.PubMedCentralCrossRefPubMed Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ: PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010, 8: e1000298-10.1371/journal.pbio.1000298.PubMedCentralCrossRefPubMed
26.
go back to reference Challa M, Malladi S, Pellock BJ, Dresnek D, Varadarajan S, Yin YW, White K, Bratton SB: Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease. Embo J. 2007, 26: 3144-3156. 10.1038/sj.emboj.7601745.PubMedCentralCrossRefPubMed Challa M, Malladi S, Pellock BJ, Dresnek D, Varadarajan S, Yin YW, White K, Bratton SB: Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease. Embo J. 2007, 26: 3144-3156. 10.1038/sj.emboj.7601745.PubMedCentralCrossRefPubMed
27.
go back to reference Liu Z, Wang X, Yu Y, Li X, Wang T, Jiang H, Ren Q, Jiao Y, Sawa A, Moran T, Ross CA, Montell C, Smith WW: A Drosophila model for LRRK2-linked parkinsonism. Proc Natl Acad Sci USA. 2008, 105: 2693-2698. 10.1073/pnas.0708452105.PubMedCentralCrossRefPubMed Liu Z, Wang X, Yu Y, Li X, Wang T, Jiang H, Ren Q, Jiao Y, Sawa A, Moran T, Ross CA, Montell C, Smith WW: A Drosophila model for LRRK2-linked parkinsonism. Proc Natl Acad Sci USA. 2008, 105: 2693-2698. 10.1073/pnas.0708452105.PubMedCentralCrossRefPubMed
28.
go back to reference Venderova K, Kabbach G, Abdel-Messih E, Zhang Y, Parks RJ, Imai Y, Gehrke S, Ngsee J, Lavoie MJ, Slack RS, Rao Y, Zhang Z, Lu B, Haque ME, Park DS: Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease. Hum Mol Genet. 2009, 18: 4390-4404. 10.1093/hmg/ddp394.CrossRefPubMed Venderova K, Kabbach G, Abdel-Messih E, Zhang Y, Parks RJ, Imai Y, Gehrke S, Ngsee J, Lavoie MJ, Slack RS, Rao Y, Zhang Z, Lu B, Haque ME, Park DS: Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease. Hum Mol Genet. 2009, 18: 4390-4404. 10.1093/hmg/ddp394.CrossRefPubMed
29.
go back to reference Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ: Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA. 2003, 100: 4078-4083. 10.1073/pnas.0737556100.PubMedCentralCrossRefPubMed Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ: Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA. 2003, 100: 4078-4083. 10.1073/pnas.0737556100.PubMedCentralCrossRefPubMed
30.
go back to reference Greene JC, Whitworth AJ, Andrews LA, Parker TJ, Pallanck LJ: Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis. Hum Mol Genet. 2005, 14: 799-811. 10.1093/hmg/ddi074.CrossRefPubMed Greene JC, Whitworth AJ, Andrews LA, Parker TJ, Pallanck LJ: Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis. Hum Mol Genet. 2005, 14: 799-811. 10.1093/hmg/ddi074.CrossRefPubMed
31.
go back to reference Lee T, Luo L: Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron. 1999, 22: 451-461. 10.1016/S0896-6273(00)80701-1.CrossRefPubMed Lee T, Luo L: Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron. 1999, 22: 451-461. 10.1016/S0896-6273(00)80701-1.CrossRefPubMed
32.
go back to reference Brand AH, Perrimon N: Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993, 118: 401-415.PubMed Brand AH, Perrimon N: Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993, 118: 401-415.PubMed
33.
go back to reference Deng H, Dodson MW, Huang H, Guo M: The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci USA. 2008, 105: 14503-14508. 10.1073/pnas.0803998105.PubMedCentralCrossRefPubMed Deng H, Dodson MW, Huang H, Guo M: The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci USA. 2008, 105: 14503-14508. 10.1073/pnas.0803998105.PubMedCentralCrossRefPubMed
34.
go back to reference Park J, Lee G, Chung J: The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process. Biochem Biophys Res Commun. 2009, 378: 518-523. 10.1016/j.bbrc.2008.11.086.CrossRefPubMed Park J, Lee G, Chung J: The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process. Biochem Biophys Res Commun. 2009, 378: 518-523. 10.1016/j.bbrc.2008.11.086.CrossRefPubMed
35.
go back to reference Aldridge AC, Benson LP, Siegenthaler MM, Whigham BT, Stowers RS, Hales KG: Roles for Drp1, a dynamin-related protein, and milton, a kinesin-associated protein, in mitochondrial segregation, unfurling and elongation during Drosophila spermatogenesis. Fly (Austin). 2007, 1: 38-46.CrossRef Aldridge AC, Benson LP, Siegenthaler MM, Whigham BT, Stowers RS, Hales KG: Roles for Drp1, a dynamin-related protein, and milton, a kinesin-associated protein, in mitochondrial segregation, unfurling and elongation during Drosophila spermatogenesis. Fly (Austin). 2007, 1: 38-46.CrossRef
36.
go back to reference Alexander C, Votruba M, Pesch UE, Thiselton DL, Mayer S, Moore A, Rodriguez M, Kellner U, Leo-Kottler B, Auburger G, Bhattacharya SS, Wissinger B: OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet. 2000, 26: 211-215. 10.1038/79944.CrossRefPubMed Alexander C, Votruba M, Pesch UE, Thiselton DL, Mayer S, Moore A, Rodriguez M, Kellner U, Leo-Kottler B, Auburger G, Bhattacharya SS, Wissinger B: OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet. 2000, 26: 211-215. 10.1038/79944.CrossRefPubMed
37.
go back to reference Yarosh W, Monserrate J, Tong JJ, Tse S, Le PK, Nguyen K, Brachmann CB, Wallace DC, Huang T: The molecular mechanisms of OPA1-mediated optic atrophy in Drosophila model and prospects for antioxidant treatment. PLoS Genet. 2008, 4: e6-10.1371/journal.pgen.0040006.PubMedCentralCrossRefPubMed Yarosh W, Monserrate J, Tong JJ, Tse S, Le PK, Nguyen K, Brachmann CB, Wallace DC, Huang T: The molecular mechanisms of OPA1-mediated optic atrophy in Drosophila model and prospects for antioxidant treatment. PLoS Genet. 2008, 4: e6-10.1371/journal.pgen.0040006.PubMedCentralCrossRefPubMed
38.
go back to reference Dai P, Akimaru H, Ishii S: A hedgehog-responsive region in the Drosophila wing disc is defined by debra-mediated ubiquitination and lysosomal degradation of Ci. Dev Cell. 2003, 4: 917-928. 10.1016/S1534-5807(03)00158-8.CrossRefPubMed Dai P, Akimaru H, Ishii S: A hedgehog-responsive region in the Drosophila wing disc is defined by debra-mediated ubiquitination and lysosomal degradation of Ci. Dev Cell. 2003, 4: 917-928. 10.1016/S1534-5807(03)00158-8.CrossRefPubMed
39.
go back to reference Bilen J, Bonini NM: Genome-wide screen for modifiers of ataxin-3 neurodegeneration in Drosophila. PLoS Genet. 2007, 3: 1950-1964. 10.1371/journal.pgen.0030177.CrossRefPubMed Bilen J, Bonini NM: Genome-wide screen for modifiers of ataxin-3 neurodegeneration in Drosophila. PLoS Genet. 2007, 3: 1950-1964. 10.1371/journal.pgen.0030177.CrossRefPubMed
40.
go back to reference Lee SJ, Koh JY: Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes. Mol Brain. 2010, 3: 30-10.1186/1756-6606-3-30.PubMedCentralCrossRefPubMed Lee SJ, Koh JY: Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes. Mol Brain. 2010, 3: 30-10.1186/1756-6606-3-30.PubMedCentralCrossRefPubMed
41.
go back to reference Weinkove D, Leevers SJ, MacDougall LK, Waterfield MD: p60 is an adaptor for the Drosophila phosphoinositide 3-kinase, Dp110. J Biol Chem. 1997, 272: 14606-14610. 10.1074/jbc.272.23.14606.CrossRefPubMed Weinkove D, Leevers SJ, MacDougall LK, Waterfield MD: p60 is an adaptor for the Drosophila phosphoinositide 3-kinase, Dp110. J Biol Chem. 1997, 272: 14606-14610. 10.1074/jbc.272.23.14606.CrossRefPubMed
42.
go back to reference Weinkove D, Neufeld TP, Twardzik T, Waterfield MD, Leevers SJ: Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor. Curr Biol. 1999, 9: 1019-1029. 10.1016/S0960-9822(99)80450-3.CrossRefPubMed Weinkove D, Neufeld TP, Twardzik T, Waterfield MD, Leevers SJ: Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor. Curr Biol. 1999, 9: 1019-1029. 10.1016/S0960-9822(99)80450-3.CrossRefPubMed
43.
go back to reference Oldham S, Stocker H, Laffargue M, Wittwer F, Wymann M, Hafen E: The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP(3) levels. Development. 2002, 129: 4103-4109.PubMed Oldham S, Stocker H, Laffargue M, Wittwer F, Wymann M, Hafen E: The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP(3) levels. Development. 2002, 129: 4103-4109.PubMed
44.
go back to reference Hietakangas V, Cohen SM: Regulation of tissue growth through nutrient sensing. Annu Rev Genet. 2009, 43: 389-410. 10.1146/annurev-genet-102108-134815.CrossRefPubMed Hietakangas V, Cohen SM: Regulation of tissue growth through nutrient sensing. Annu Rev Genet. 2009, 43: 389-410. 10.1146/annurev-genet-102108-134815.CrossRefPubMed
45.
go back to reference Liu S, Lu B: Reduction of protein translation and activation of autophagy protect against PINK1 pathogenesis in Drosophila melanogaster. PLoS Genet. 2010, 6: e1001237-10.1371/journal.pgen.1001237.PubMedCentralCrossRefPubMed Liu S, Lu B: Reduction of protein translation and activation of autophagy protect against PINK1 pathogenesis in Drosophila melanogaster. PLoS Genet. 2010, 6: e1001237-10.1371/journal.pgen.1001237.PubMedCentralCrossRefPubMed
46.
go back to reference Tain LS, Mortiboys H, Tao RN, Ziviani E, Bandmann O, Whitworth AJ: Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat Neurosci. 2009, 12: 1129-1135. 10.1038/nn.2372.PubMedCentralCrossRefPubMed Tain LS, Mortiboys H, Tao RN, Ziviani E, Bandmann O, Whitworth AJ: Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat Neurosci. 2009, 12: 1129-1135. 10.1038/nn.2372.PubMedCentralCrossRefPubMed
47.
go back to reference Haines N, Irvine KD: Functional analysis of Drosophila beta1,4-N-acetlygalactosaminyltransferases. Glycobiology. 2005, 15: 335-346. 10.1093/glycob/cwi017.CrossRefPubMed Haines N, Irvine KD: Functional analysis of Drosophila beta1,4-N-acetlygalactosaminyltransferases. Glycobiology. 2005, 15: 335-346. 10.1093/glycob/cwi017.CrossRefPubMed
48.
go back to reference Haines N, Stewart BA: Functional roles for beta1,4-N-acetlygalactosaminyltransferase-A in Drosophila larval neurons and muscles. Genetics. 2007, 175: 671-679. 10.1534/genetics.106.065565.PubMedCentralCrossRefPubMed Haines N, Stewart BA: Functional roles for beta1,4-N-acetlygalactosaminyltransferase-A in Drosophila larval neurons and muscles. Genetics. 2007, 175: 671-679. 10.1534/genetics.106.065565.PubMedCentralCrossRefPubMed
49.
go back to reference Ohtsubo K, Marth JD: Glycosylation in cellular mechanisms of health and disease. Cell. 2006, 126: 855-867. 10.1016/j.cell.2006.08.019.CrossRefPubMed Ohtsubo K, Marth JD: Glycosylation in cellular mechanisms of health and disease. Cell. 2006, 126: 855-867. 10.1016/j.cell.2006.08.019.CrossRefPubMed
50.
go back to reference Longman C, Brockington M, Torelli S, Jimenez-Mallebrera C, Kennedy C, Khalil N, Feng L, Saran RK, Voit T, Merlini L, Sewry CA, Brown SC, Muntoni F: Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. Hum Mol Genet. 2003, 12: 2853-2861. 10.1093/hmg/ddg307.CrossRefPubMed Longman C, Brockington M, Torelli S, Jimenez-Mallebrera C, Kennedy C, Khalil N, Feng L, Saran RK, Voit T, Merlini L, Sewry CA, Brown SC, Muntoni F: Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. Hum Mol Genet. 2003, 12: 2853-2861. 10.1093/hmg/ddg307.CrossRefPubMed
51.
go back to reference Dei R, Takeda A, Niwa H, Li M, Nakagomi Y, Watanabe M, Inagaki T, Washimi Y, Yasuda Y, Horie K, Miyata T, Sobue G: Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease. Acta Neuropathol. 2002, 104: 113-122. 10.1007/s00401-002-0523-y.CrossRefPubMed Dei R, Takeda A, Niwa H, Li M, Nakagomi Y, Watanabe M, Inagaki T, Washimi Y, Yasuda Y, Horie K, Miyata T, Sobue G: Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease. Acta Neuropathol. 2002, 104: 113-122. 10.1007/s00401-002-0523-y.CrossRefPubMed
Metadata
Title
Genome-wide screen for modifiers of Parkinson's disease genes in Drosophila
Authors
Caroline Fernandes
Yong Rao
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Brain / Issue 1/2011
Electronic ISSN: 1756-6606
DOI
https://doi.org/10.1186/1756-6606-4-17

Other articles of this Issue 1/2011

Molecular Brain 1/2011 Go to the issue