A systematic analysis of protein palmitoylation in Caenorhabditis elegans

详细信息    查看全文

• 作者：Matthew J Edmonds (10)
  Alan Morgan (10)
  
  10. Department of Cellular and Molecular Physiology ; Institute of Translational Medicine ; University of Liverpool ; Crown St. ; Liverpool ; L69 3BX ; UK
  
• 关键词：DHHC ; Palmitoyl acyl ; transferase ; Palmitoyl ; protein thioesterase ; Neuronal ceroid lipofuscinosis
• 刊名：BMC Genomics
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：15
• 期：1
• 全文大小：1,884 KB
• 参考文献：1. Mitchell, DA, Vasudevan, A, Linder, ME, Deschenes, RJ (2006) Protein palmitoylation by a family of DHHC protein S-acyltransferases. J Lipid Res 47: pp. 1118-1127 10.1194/jlr.R600007-JLR200" target="_blank" title="It opens in new window">CrossRef
  2. Camp, LA, Verkruyse, LA, Afendis, SJ, Slaughter, CA, Hofmann, SL (1994) Molecular cloning and expression of palmitoyl-protein thioesterase. J Biol Chem 269: pp. 23212-23219
  3. Soyombo, AA, Hofmann, SL (1997) Molecular cloning and expression of palmitoyl-protein thioesterase 2 (PPT2), a homolog of lysosomal palmitoyl-protein thioesterase with a distinct substrate specificity. J Biol Chem 272: pp. 27456-27463 10.1074/jbc.272.43.27456" target="_blank" title="It opens in new window">CrossRef
  4. Fukata, Y, Fukata, M (2010) Protein palmitoylation in neuronal development and synaptic plasticity. Nat Rev Neurosci 11: pp. 161-175 10.1038/nrn2788" target="_blank" title="It opens in new window">CrossRef
  5. Greaves, J, Chamberlain, LH (2011) DHHC palmitoyl transferases: substrate interactions and (patho)physiology. Trends Biochem Sci 36: pp. 245-253 10.1016/j.tibs.2011.01.003" target="_blank" title="It opens in new window">CrossRef
  6. Korycka, J, Lach, A, Heger, E, Boguslawska, DM, Wolny, M, Toporkiewicz, M, Augoff, K, Korzeniewski, J, Sikorski, AF (2012) Human DHHC proteins: a spotlight on the hidden player of palmitoylation. Eur J Cell Biol 91: pp. 107-117 10.1016/j.ejcb.2011.09.013" target="_blank" title="It opens in new window">CrossRef
  7. Omary, MB, Trowbridge, IS (1981) Covalent binding of fatty acid to the transferrin receptor in cultured human cells. J Biol Chem 256: pp. 4715-4718
  8. Bohm, S, Frishman, D, Mewes, HW (1997) Variations of the C2H2 zinc finger motif in the yeast genome and classification of yeast zinc finger proteins. Nucleic Acids Res 25: pp. 2464-2469 10.1093/nar/25.12.2464" target="_blank" title="It opens in new window">CrossRef
  9. Fukata, M, Fukata, Y, Adesnik, H, Nicoll, RA, Bredt, DS (2004) Identification of PSD-95 palmitoylating enzymes. Neuron 44: pp. 987-996 10.1016/j.neuron.2004.12.005" target="_blank" title="It opens in new window">CrossRef
  10. Roth, AF, Feng, Y, Chen, L, Davis, NG (2002) The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase. J Cell Biol 159: pp. 23-28 10.1083/jcb.200206120" target="_blank" title="It opens in new window">CrossRef
  11. Bannan, BA, Van Etten, J, Kohler, JA, Tsoi, Y, Hansen, NM, Sigmon, S, Fowler, E, Buff, H, Williams, TS, Ault, JG, Glaser, RL, Korey, CA (2008) The Drosophila protein palmitoylome: characterizing palmitoyl-thioesterases and DHHC palmitoyl-transferases. Fly (Austin) 2: pp. 198-214 10.4161/fly.6621" target="_blank" title="It opens in new window">CrossRef
  12. Mitchell, DA, Mitchell, G, Ling, Y, Budde, C, Deschenes, RJ (2010) Mutational analysis of Saccharomyces cerevisiae Erf2 reveals a two-step reaction mechanism for protein palmitoylation by DHHC enzymes. J Biol Chem 285: pp. 38104-38114 10.1074/jbc.M110.169102" target="_blank" title="It opens in new window">CrossRef
  13. Ohno, Y, Kashio, A, Ogata, R, Ishitomi, A, Yamazaki, Y, Kihara, A (2012) Analysis of substrate specificity of human DHHC protein acyltransferases using a yeast expression system. Mol Biol Cell 23: pp. 4543-4551 10.1091/mbc.E12-05-0336" target="_blank" title="It opens in new window">CrossRef
  14. Duncan, JA, Gilman, AG (1998) A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS). J Biol Chem 273: pp. 15830-15837 10.1074/jbc.273.25.15830" target="_blank" title="It opens in new window">CrossRef
  15. Camp, LA, Hofmann, SL (1993) Purification and properties of a palmitoyl-protein thioesterase that cleaves palmitate from H-Ras. J Biol Chem 268: pp. 22566-22574
  16. Verkruyse, LA, Hofmann, SL (1996) Lysosomal targeting of palmitoyl-protein thioesterase. J Biol Chem 271: pp. 15831-15836 10.1074/jbc.271.26.15831" target="_blank" title="It opens in new window">CrossRef
  17. Lehtovirta, M, Kyttala, A, Eskelinen, EL, Hess, M, Heinonen, O, Jalanko, A (2001) Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons: implications for infantile neuronal ceroid lipofuscinosis (INCL). Hum Mol Genet 10: pp. 69-75 10.1093/hmg/10.1.69" target="_blank" title="It opens in new window">CrossRef
  18. Calero, G, Gupta, P, Nonato, MC, Tandel, S, Biehl, ER, Hofmann, SL, Clardy, J (2003) The crystal structure of palmitoyl protein thioesterase-2 (PPT2) reveals the basis for divergent substrate specificities of the two lysosomal thioesterases, PPT1 and PPT2. J Biol Chem 278: pp. 37957-37964 10.1074/jbc.M301225200" target="_blank" title="It opens in new window">CrossRef
  19. Kang, R, Wan, J, Arstikaitis, P, Takahashi, H, Huang, K, Bailey, AO, Thompson, JX, Roth, AF, Drisdel, RC, Mastro, R, Green, WN, Yates, JR, Davis, NG, El-Husseini, A (2008) Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation. Nature 456: pp. 904-909 10.1038/nature07605" target="_blank" title="It opens in new window">CrossRef
  20. Roth, AF, Wan, J, Bailey, AO, Sun, B, Kuchar, JA, Green, WN, Phinney, BS, Yates, JR, Davis, NG (2006) Global analysis of protein palmitoylation in yeast. Cell 125: pp. 1003-1013 10.1016/j.cell.2006.03.042" target="_blank" title="It opens in new window">CrossRef
  21. Yang, W, Di Vizio, D, Kirchner, M, Steen, H, Freeman, MR (2010) Proteome scale characterization of human S-acylated proteins in lipid raft-enriched and non-raft membranes. Mol Cell Proteomics 9: pp. 54-70 10.1074/mcp.M800448-MCP200" target="_blank" title="It opens in new window">CrossRef
  22. Dowal, L, Yang, W, Freeman, MR, Steen, H, Flaumenhaft, R (2011) Proteomic analysis of palmitoylated platelet proteins. Blood 118: pp. e62-73 10.1182/blood-2011-05-353078" target="_blank" title="It opens in new window">CrossRef
  23. Marin, EP, Derakhshan, B, Lam, TT, Davalos, A, Sessa, WC (2012) Endothelial cell palmitoylproteomic identifies novel lipid-modified targets and potential substrates for protein acyl transferases. Circ Res 110: pp. 1336-1344 10.1161/CIRCRESAHA.112.269514" target="_blank" title="It opens in new window">CrossRef
  24. Merrick, BA, Dhungana, S, Williams, JG, Aloor, JJ, Peddada, S, Tomer, KB, Fessler, MB (2011) Proteomic profiling of S-acylated macrophage proteins identifies a role for palmitoylation in mitochondrial targeting of phospholipid scramblase 3. Mol Cell Proteomics 10: pp. M110 006007 10.1074/mcp.M110.006007" target="_blank" title="It opens in new window">CrossRef
  25. Kamath, RS, Martinez-Campos, M, Zipperlen, P, Fraser, AG, Ahringer, J (2001) Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans. Genome Biol.
  26. Timmons, L, Fire, A (1998) Specific interference by ingested dsRNA. Nature 395: pp. 854 10.1038/27579" target="_blank" title="It opens in new window">CrossRef
  27. Gleason, EJ, Lindsey, WC, Kroft, TL, Singson, AW, L鈥橦ernault, SW (2006) spe-10 encodes a DHHC-CRD zinc-finger membrane protein required for endoplasmic reticulum/Golgi membrane morphogenesis during Caenorhabditis elegans spermatogenesis. Genetics 172: pp. 145-158 10.1534/genetics.105.047340" target="_blank" title="It opens in new window">CrossRef
  28. Shakes, DC, Ward, S (1989) Mutations that disrupt the morphogenesis and localization of a sperm-specific organelle in Caenorhabditis elegans. Dev Biol 134: pp. 307-316 10.1016/0012-1606(89)90103-6" target="_blank" title="It opens in new window">CrossRef
  29. Cypser, JR, Johnson, TE (1999) The spe-10 mutant has longer life and increased stress resistance. Neurobiol Aging 20: pp. 503-512 10.1016/S0197-4580(99)00085-8" target="_blank" title="It opens in new window">CrossRef
  30. Porter, MY, Turmaine, M, Mole, SE (2005) Identification and characterization of Caenorhabditis elegans palmitoyl protein thioesterase1. J Neurosci Res 79: pp. 836-848 10.1002/jnr.20403" target="_blank" title="It opens in new window">CrossRef
  31. Vesa, J, Hellsten, E, Verkruyse, LA, Camp, LA, Rapola, J, Santavuori, P, Hofmann, SL, Peltonen, L (1995) Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature 376: pp. 584-587 10.1038/376584a0" target="_blank" title="It opens in new window">CrossRef
  32. Brenner, S (1974) The genetics of Caenorhabditis elegans. Genetics 77: pp. 71-94
  33. Chalfie, M, Sulston, J (1981) Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans. Dev Biol 82: pp. 358-370 10.1016/0012-1606(81)90459-0" target="_blank" title="It opens in new window">CrossRef
  34. Prescott, GR, Gorleku, OA, Greaves, J, Chamberlain, LH (2009) Palmitoylation of the synaptic vesicle fusion machinery. J Neurochem 110: pp. 1135-1149 10.1111/j.1471-4159.2009.06205.x" target="_blank" title="It opens in new window">CrossRef
  35. Kihara, A, Kurotsu, F, Sano, T, Iwaki, S, Igarashi, Y (2005) Long-chain base kinase Lcb4 Is anchored to the membrane through its palmitoylation by Akr1. Mol Cell Biol 25: pp. 9189-9197 10.1128/MCB.25.21.9189-9197.2005" target="_blank" title="It opens in new window">CrossRef
  36. Gonzalez Montoro, A, Quiroga, R, Maccioni, HJ, Valdez Taubas, J (2009) A novel motif at the C-terminus of palmitoyltransferases is essential for Swf1 and Pfa3 function in vivo. Biochem J 419: pp. 301-308 10.1042/BJ20080921" target="_blank" title="It opens in new window">CrossRef
  37. Huang, K, Sanders, S, Singaraja, R, Orban, P, Cijsouw, T, Arstikaitis, P, Yanai, A, Hayden, MR, El-Husseini, A (2009) Neuronal palmitoyl acyl transferases exhibit distinct substrate specificity. FASEB J 23: pp. 2605-2615 10.1096/fj.08-127399" target="_blank" title="It opens in new window">CrossRef
  38. Huh, WK, Falvo, JV, Gerke, LC, Carroll, AS, Howson, RW, Weissman, JS, O鈥橲hea, EK (2003) Global analysis of protein localization in budding yeast. Nature 425: pp. 686-691 10.1038/nature02026" target="_blank" title="It opens in new window">CrossRef
  39. Rual, JF, Ceron, J, Koreth, J, Hao, T, Nicot, AS, Hirozane-Kishikawa, T, Vandenhaute, J, Orkin, SH, Hill, DE, van den Heuvel, S, Vidal, M (2004) Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res 14: pp. 2162-2168 10.1101/gr.2505604" target="_blank" title="It opens in new window">CrossRef
  40. Fire, A, Xu, S, Montgomery, MK, Kostas, SA, Driver, SE, Mello, CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: pp. 806-811 10.1038/35888" target="_blank" title="It opens in new window">CrossRef
  41. Simmer, F, Tijsterman, M, Parrish, S, Koushika, SP, Nonet, ML, Fire, A, Ahringer, J, Plasterk, RH (2002) Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi. Curr Biol 12: pp. 1317-1319 10.1016/S0960-9822(02)01041-2" target="_blank" title="It opens in new window">CrossRef
  42. Brown, AE, Yemini, EI, Grundy, LJ, Jucikas, T, Schafer, WR (2013) A dictionary of behavioral motifs reveals clusters of genes affecting Caenorhabditis elegans locomotion. Proc Natl Acad Sci U S A 110: pp. 791-796 10.1073/pnas.1211447110" target="_blank" title="It opens in new window">CrossRef
  43. Yemini, E, Jucikas, T, Grundy, LJ, Brown, AE, Schafer, WR (2013) A database of Caenorhabditis elegans behavioral phenotypes. Nat Methods 10: pp. 877-879 10.1038/nmeth.2560" target="_blank" title="It opens in new window">CrossRef
  44. Johnson, JR, Ferdek, P, Lian, LY, Barclay, JW, Burgoyne, RD, Morgan, A (2009) Binding of UNC-18 to the N-terminus of syntaxin is essential for neurotransmission in Caenorhabditis elegans. Biochem J 418: pp. 73-80 10.1042/BJ20081956" target="_blank" title="It opens in new window">CrossRef
  45. Miller, KG, Emerson, MD, Rand, JB (1999) Goalpha and diacylglycerol kinase negatively regulate the Gqalpha pathway in C. elegans. Neuron 24: pp. 323-333 10.1016/S0896-6273(00)80847-8" target="_blank" title="It opens in new window">CrossRef
  46. Rush, DB, Leon, RT, McCollum, MH, Treu, RW, Wei, J (2012) Palmitoylation and trafficking of GAD65 are impaired in a cellular model of Huntington鈥檚 disease. Biochem J 442: pp. 39-48 10.1042/BJ20110679" target="_blank" title="It opens in new window">CrossRef
  47. Velinov, M, Dolzhanskaya, N, Gonzalez, M, Powell, E, Konidari, I, Hulme, W, Staropoli, JF, Xin, W, Wen, GY, Barone, R, Coppel, SH, Sims, K, Brown, WT, Zuchner, S (2012) Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families. PLoS One 7: pp. e29729 10.1371/journal.pone.0029729" target="_blank" title="It opens in new window">CrossRef
  48. Vetrivel, KS, Meckler, X, Chen, Y, Nguyen, PD, Seidah, NG, Vassar, R, Wong, PC, Fukata, M, Kounnas, MZ, Thinakaran, G (2009) Alzheimer disease Abeta production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid rafts. J Biol Chem 284: pp. 3793-3803 10.1074/jbc.M808920200" target="_blank" title="It opens in new window">CrossRef
  49. Das, AK, Lu, JY, Hofmann, SL (2001) Biochemical analysis of mutations in palmitoyl-protein thioesterase causing infantile and late-onset forms of neuronal ceroid lipofuscinosis. Hum Mol Genet 10: pp. 1431-1439 10.1093/hmg/10.13.1431" target="_blank" title="It opens in new window">CrossRef
  50. Singaraja, RR, Huang, K, Sanders, SS, Milnerwood, AJ, Hines, R, Lerch, JP, Franciosi, S, Drisdel, RC, Vaid, K, Young, FB, Doty, C, Wan, J, Bissada, N, Henkelman, RM, Green, WN, Davis, NG, Raymond, LA, Hayden, MR (2011) Altered palmitoylation and neuropathological deficits in mice lacking HIP14. Hum Mol Genet 20: pp. 3899-3909 10.1093/hmg/ddr308" target="_blank" title="It opens in new window">CrossRef
  51. Sutton, LM, Sanders, SS, Butland, SL, Singaraja, RR, Franciosi, S, Southwell, AL, Doty, CN, Schmidt, ME, Mui, KK, Kovalik, V, Young, FB, Zhang, W, Hayden, MR (2013) Hip14l-deficient mice develop neuropathological and behavioural features of Huntington disease. Hum Mol Genet 22: pp. 452-465 10.1093/hmg/dds441" target="_blank" title="It opens in new window">CrossRef
  52. Gouda, K, Matsunaga, Y, Iwasaki, T, Kawano, T (2010) An altered method of feeding RNAi that knocks down multiple genes simultaneously in the nematode Caenorhabditis elegans. Biosci Biotechnol Biochem 74: pp. 2361-2365 10.1271/bbb.100579" target="_blank" title="It opens in new window">CrossRef
  53. Min, K, Kang, J, Lee, J (2010) A modified feeding RNAi method for simultaneous knock-down of more than one gene in Caenorhabditis elegans. Biotechniques 48: pp. 229-232 10.2144/000113365" target="_blank" title="It opens in new window">CrossRef
  54. Lobo, S, Greentree, WK, Linder, ME, Deschenes, RJ (2002) Identification of a Ras palmitoyltransferase in Saccharomyces cerevisiae. J Biol Chem 277: pp. 41268-41273 10.1074/jbc.M206573200" target="_blank" title="It opens in new window">CrossRef
  55. Simmer, F, Moorman, C, van der Linden, AM, Kuijk, E, van den Berghe, PV, Kamath, RS, Fraser, AG, Ahringer, J, Plasterk, RH (2003) Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol 1: pp. E12 10.1371/journal.pbio.0000012" target="_blank" title="It opens in new window">CrossRef
  56. Greaves, J, Gorleku, OA, Salaun, C, Chamberlain, LH (2010) Palmitoylation of the SNAP25 protein family: specificity and regulation by DHHC palmitoyl transferases. J Biol Chem 285: pp. 24629-24638 10.1074/jbc.M110.119289" target="_blank" title="It opens in new window">CrossRef
  57. Hou, H, John, PAT, Meiringer, C, Subramanian, K, Ungermann, C (2009) Analysis of DHHC acyltransferases implies overlapping substrate specificity and a two-step reaction mechanism. Traffic 10: pp. 1061-1073 10.1111/j.1600-0854.2009.00925.x" target="_blank" title="It opens in new window">CrossRef
  58. Stowers, RS, Isacoff, EY (2007) Drosophila huntingtin-interacting protein 14 is a presynaptic protein required for photoreceptor synaptic transmission and expression of the palmitoylated proteins synaptosome-associated protein 25 and cysteine string protein. J Neurosci 27: pp. 12874-12883 10.1523/JNEUROSCI.2464-07.2007" target="_blank" title="It opens in new window">CrossRef
  59. Ohyama, T, Verstreken, P, Ly, CV, Rosenmund, T, Rajan, A, Tien, AC, Haueter, C, Schulze, KL, Bellen, HJ (2007) Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles. J Cell Biol 179: pp. 1481-1496 10.1083/jcb.200710061" target="_blank" title="It opens in new window">CrossRef
  60. Zinsmaier, KE, Eberle, KK, Buchner, E, Walter, N, Benzer, S (1994) Paralysis and early death in cysteine string protein mutants of Drosophila. Science 263: pp. 977-980 10.1126/science.8310297" target="_blank" title="It opens in new window">CrossRef
  61. Kashyap, SS, Johnson, JR, McCue, HV, Chen, X, Edmonds, MJ, Ayala, M, Graham, ME, Jenn, RC, Barclay, JW, Burgoyne, RD, Morgan, A (2014) Caenorhabditis elegans dnj-14, the orthologue of the DNAJC5 gene mutated in adult onset neuronal ceroid lipofuscinosis, provides a new platform for neuroprotective drug screening and identifies a SIR-2.1-independent action of resveratrol. Hum Mol Genet.
  62. Bellizzi, JJ, Widom, J, Kemp, C, Lu, JY, Das, AK, Hofmann, SL, Clardy, J (2000) The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis. Proc Natl Acad Sci U S A 97: pp. 4573-4578 10.1073/pnas.080508097" target="_blank" title="It opens in new window">CrossRef
  63. Devedjiev, Y, Dauter, Z, Kuznetsov, SR, Jones, TL, Derewenda, ZS (2000) Crystal structure of the human acyl protein thioesterase I from a single X-ray data set to 1.5 A. Structure 8: pp. 1137-1146 10.1016/S0969-2126(00)00529-3" target="_blank" title="It opens in new window">CrossRef
  64. Manning, G, Whyte, DB, Martinez, R, Hunter, T, Sudarsanam, S (2002) The protein kinase complement of the human genome. Science 298: pp. 1912-1934 10.1126/science.1075762" target="_blank" title="It opens in new window">CrossRef
  65. Sacco, F, Perfetto, L, Castagnoli, L, Cesareni, G (2012) The human phosphatase interactome: An intricate family portrait. FEBS Lett 586: pp. 2732-2739 10.1016/j.febslet.2012.05.008" target="_blank" title="It opens in new window">CrossRef
  66. Li, W, Bengtson, MH, Ulbrich, A, Matsuda, A, Reddy, VA, Orth, A, Chanda, SK, Batalov, S, Joazeiro, CA (2008) Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle鈥檚 dynamics and signaling. PLoS One 3: pp. e1487 10.1371/journal.pone.0001487" target="_blank" title="It opens in new window">CrossRef
  67. Clague, MJ, Coulson, JM, Urbe, S (2012) Cellular functions of the DUBs. J Cell Sci 125: pp. 277-286 10.1242/jcs.090985" target="_blank" title="It opens in new window">CrossRef
  68. Duncan, JA, Gilman, AG (2002) Characterization of Saccharomyces cerevisiae acyl-protein thioesterase 1, the enzyme responsible for G protein alpha subunit deacylation in vivo. J Biol Chem 277: pp. 31740-31752 10.1074/jbc.M202505200" target="_blank" title="It opens in new window">CrossRef
  69. Dekker, FJ, Rocks, O, Vartak, N, Menninger, S, Hedberg, C, Balamurugan, R, Wetzel, S, Renner, S, Gerauer, M, Scholermann, B, Rusch, M, Kramer, JW, Rauh, D, Coates, GW, Brunsveld, L, Bastiaens, PI, Waldmann, H (2010) Small-molecule inhibition of APT1 affects Ras localization and signaling. Nat Chem Biol 6: pp. 449-456 10.1038/nchembio.362" target="_blank" title="It opens in new window">CrossRef
  70. Tian, L, McClafferty, H, Knaus, HG, Ruth, P, Shipston, MJ (2012) Distinct acyl protein transferases and thioesterases control surface expression of calcium-activated potassium channels. J Biol Chem 287: pp. 14718-14725 10.1074/jbc.M111.335547" target="_blank" title="It opens in new window">CrossRef
  71. Letunic, I, Bork, P (2007) Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics 23: pp. 127-128 10.1093/bioinformatics/btl529" target="_blank" title="It opens in new window">CrossRef
  72. Timmons, L, Court, DL, Fire, A (2001) Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263: pp. 103-112 10.1016/S0378-1119(00)00579-5" target="_blank" title="It opens in new window">CrossRef
  73. Yang, JS, Nam, HJ, Seo, M, Han, SK, Choi, Y, Nam, HG, Lee, SJ, Kim, S (2011) OASIS: online application for the survival analysis of lifespan assays performed in aging research. PLoS One 6: pp. e23525 10.1371/journal.pone.0023525" target="_blank" title="It opens in new window">CrossRef
  
• 刊物主题：Life Sciences, general; Microarrays; Proteomics; Animal Genetics and Genomics; Microbial Genetics and Genomics; Plant Genetics & Genomics;
• 出版者：BioMed Central
• ISSN：1471-2164

文摘

Background Palmitoylation is a reversible post-translational protein modification which involves the addition of palmitate to cysteine residues. Palmitoylation is catalysed by the DHHC family of palmitoyl-acyl transferases (PATs) and reversibility is conferred by palmitoyl-protein thioesterases (PPTs). Mutations in genes encoding both classes of enzymes are associated with human diseases, notably neurological disorders, underlining their importance. Despite the pivotal role of yeast studies in discovering PATs, palmitoylation has not been studied in the key animal model Caenorhabditis elegans. Results Analysis of the C. elegans genome identified fifteen PATs, using the DHHC cysteine-rich domain, and two PPTs, by homology. The twelve uncategorised PATs were officially named using a dhhc-x system. Genomic data on these palmitoylation enzymes and those in yeast, Drosophila and humans was collated and analysed to predict properties and relationships in C. elegans. All available C. elegans strains containing a mutation in a palmitoylation enzyme were analysed and a complete library of RNA interference (RNAi) feeding plasmids against PAT or PPT genes was generated. To test for possible redundancy, double RNAi was performed against selected closely related PATs and both PPTs. Animals were screened for phenotypes including size, longevity and sensory and motor neuronal functions. Although some significant differences were observed with individual mutants or RNAi treatment, in general there was little impact on these phenotypes, suggesting that genetic buffering exists within the palmitoylation network in worms. Conclusions This study reports the first characterisation of palmitoylation in C. elegans using both in silico and in vivo approaches, and opens up this key model organism for further detailed study of palmitoylation in future.