#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Promotion of Bone Morphogenetic Protein Signaling by Tetraspanins and Glycosphingolipids


The bone morphogenetic protein (BMP) signaling pathway is required for multiple developmental processes during metazoan development. Various diseases, including cancer, can result from mis-regulation of the BMP pathway. Thus, it is critical to identify factors that ensure proper regulation of BMP signaling. Using the nematode C. elegans, we have devised a highly specific and sensitive genetic screen to identify new modulators in the BMP pathway. Through this screen, we identified three conserved tetraspanin molecules as novel factors that function to promote BMP signaling in a living organism. We further showed that these three tetraspanins likely form a complex and function together with glycosphingolipids to promote BMP signaling. Recent studies have implicated several tetraspanins in cancer initiation, progression and metastasis in mammals. Our findings suggest that the involvement of tetraspanins in cancer may partially be due to their function in modulating the activity of BMP signaling.


Vyšlo v časopise: Promotion of Bone Morphogenetic Protein Signaling by Tetraspanins and Glycosphingolipids. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005221
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005221

Souhrn

The bone morphogenetic protein (BMP) signaling pathway is required for multiple developmental processes during metazoan development. Various diseases, including cancer, can result from mis-regulation of the BMP pathway. Thus, it is critical to identify factors that ensure proper regulation of BMP signaling. Using the nematode C. elegans, we have devised a highly specific and sensitive genetic screen to identify new modulators in the BMP pathway. Through this screen, we identified three conserved tetraspanin molecules as novel factors that function to promote BMP signaling in a living organism. We further showed that these three tetraspanins likely form a complex and function together with glycosphingolipids to promote BMP signaling. Recent studies have implicated several tetraspanins in cancer initiation, progression and metastasis in mammals. Our findings suggest that the involvement of tetraspanins in cancer may partially be due to their function in modulating the activity of BMP signaling.


Zdroje

1. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003;113:685–700. 12809600

2. Wu MY, Hill CS. Tgf-beta superfamily signaling in embryonic development and homeostasis. Dev Cell 2009;16:329–43. doi: 10.1016/j.devcel.2009.02.012 19289080

3. Constam DB. Regulation of TGFbeta and related signals by precursor processing. Semin Cell Dev Biol 2014;32:85–97. doi: 10.1016/j.semcdb.2014.01.008 24508081

4. Gordon KJ, Blobe GC. Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta 2008;1782:197–228. doi: 10.1016/j.bbadis.2008.01.006 18313409

5. Cai J, Pardali E, Sanchez-Duffhues G, ten Dijke P. BMP signaling in vascular diseases. FEBS Lett 2012;586:1993–2002. doi: 10.1016/j.febslet.2012.04.030 22710160

6. Massague J. TGFbeta in Cancer. Cell 2008;134:215–30. doi: 10.1016/j.cell.2008.07.001 18662538

7. Massague J. TGF-beta signaling in development and disease. FEBS Lett 2012;586:1833. doi: 10.1016/j.febslet.2012.05.030 22651913

8. Moustakas A, Heldin CH. The regulation of TGFbeta signal transduction. Development 2009;136:3699–714. doi: 10.1242/dev.030338 19855013

9. Umulis D, O'Connor MB, Blair SS. The extracellular regulation of bone morphogenetic protein signaling. Development 2009;136:3715–28. doi: 10.1242/dev.031534 19855014

10. Massague J. TGFbeta signaling in context. Nat Rev Mol Cell Biol 2012;13:616–30. doi: 10.1038/nrm3434 22992590

11. Ramel MC, Hill CS. Spatial regulation of BMP activity. FEBS Lett 2012;586:1929–41. doi: 10.1016/j.febslet.2012.02.035 22710177

12. Gumienny TL, Savage-Dunn C. TGF-beta signaling in C. elegans. WormBook 2013;:1–34.

13. Morita K, Flemming AJ, Sugihara Y, Modhii M, Suzuki Y, Yoshida S, et al. A Caenorhabditis elegans TGF-beta, DBL-1, controls the expression of LON-1, a PR-related protein, that regulates polyploidization and body length. EMBO J 2002;21:1063–73. 11867534

14. Suzuki Y, Yandell MD, Roy PJ, Krishna S, Savage-Dunn C, Ross RM, et al. A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans. Development 1999;126:241–50. 9847238

15. Krishna S, Maduzia LL, Padgett RW. Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans. Development 1999;126:251–60. 9847239

16. Estevez M, Attisano L, Wrana JL, Albert PS, Massague J, Riddle DL. The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development. Nature 1993;365:644–9. 8413626

17. Savage C, Das P, Finelli AL, Townsend SR, Sun CY, Baird SE, et al. Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components. Proc Natl Acad Sci U S A 1996;93:790–4. 8570636

18. Sulston JE, Horvitz HR. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 1977;56:110–56. 838129

19. Liang J, Lints R, Foehr ML, Tokarz R, Yu L, Emmons SW, et al. The Caenorhabditis elegans schnurri homolog sma-9 mediates stage- and cell type-specific responses to DBL-1 BMP-related signaling. Development 2003;130:6453–64. 14627718

20. Foehr ML, Lindy AS, Fairbank RC, Amin NM, Xu M, Yanowitz J, et al. An antagonistic role for the C. elegans Schnurri homolog SMA-9 in modulating TGFbeta signaling during mesodermal patterning. Development 2006;133:2887–96. 16790477

21. Tian C, Sen D, Shi H, Foehr ML, Plavskin Y, Vatamaniuk OK, et al. The RGM protein DRAG-1 positively regulates a BMP-like signaling pathway in Caenorhabditis elegans. Development 2010;137:2375–84. doi: 10.1242/dev.051615 20534671

22. Tian C, Shi H, Xiong S, Hu F, Xiong WC, Liu J. The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein DRAG-1 in C. elegans. Development 2013;140:4070–80. doi: 10.1242/dev.099838 24004951

23. Tian C, Liu J. Repulsive guidance molecules (RGMs) and neogenin in bone morphogenetic protein (BMP) signaling. Mol Reprod Dev 2013;80:700–17. doi: 10.1002/mrd.22199 23740870

24. Hemler ME. Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol 2005;6:801–11. 16314869

25. Charrin S, le Naour F, Silvie O, Milhiet PE, Boucheix C, Rubinstein E. Lateral organization of membrane proteins: tetraspanins spin their web. Biochem J 2009;420:133–54. doi: 10.1042/BJ20082422 19426143

26. Yanez-Mo M, Barreiro O, Gordon-Alonso M, Sala-Valdes M, Sanchez-Madrid F. Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes. Trends Cell Biol 2009;19:434–46. doi: 10.1016/j.tcb.2009.06.004 19709882

27. Zoller M. Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer 2009;9:40–55. doi: 10.1038/nrc2543 19078974

28. Dunn CD, Sulis ML, Ferrando AA, Greenwald I. A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells. Proc Natl Acad Sci U S A 2010;107:5907–12. doi: 10.1073/pnas.1001647107 20220101

29. Colavita A, Krishna S, Zheng H, Padgett RW, Culotti JG. Pioneer axon guidance by UNC-129, a C. elegans TGF-beta. Science 1998;281:706–9. 9685266

30. McKeown C, Praitis V, Austin J. sma-1 encodes a betaH-spectrin homolog required for Caenorhabditis elegans morphogenesis. Development 1998;125:2087–98. 9570773

31. Nystrom J, Shen ZZ, Aili M, Flemming AJ, Leroi A, Tuck S. Increased or decreased levels of Caenorhabditis elegans lon-3, a gene encoding a collagen, cause reciprocal changes in body length. Genetics 2002;161:83–97. 12019225

32. Suzuki Y, Morris GA, Han M, Wood WB. A cuticle collagen encoded by the lon-3 gene may be a target of TGF-beta signaling in determining Caenorhabditis elegans body shape. Genetics 2002;162:1631–9. 12524338

33. Amin NM, Shi H, Liu J. The FoxF/FoxC factor LET-381 directly regulates both cell fate specification and cell differentiation in C. elegans mesoderm development. Development 2010;137:1451–60. doi: 10.1242/dev.048496 20335356

34. Gumienny TL, Macneil L, Zimmerman CM, Wang H, Chin L, Wrana JL, et al. Caenorhabditis elegans SMA-10/LRIG is a conserved transmembrane protein that enhances bone morphogenetic protein signaling. PLoS Genet 2010;6:e1000963. doi: 10.1371/journal.pgen.1000963 20502686

35. Maduzia LL, Gumienny TL, Zimmerman CM, Wang H, Shetgiri P, Krishna S, et al. lon-1 regulates Caenorhabditis elegans body size downstream of the dbl-1 TGF beta signaling pathway. Dev Biol 2002;246:418–28. 12051826

36. DeSalle R, Mares R, Garcia-Espana A. Evolution of cysteine patterns in the large extracellular loop of tetraspanins from animals, fungi, plants and single-celled eukaryotes. Mol Phylogenet Evol 2010;56:486–91. doi: 10.1016/j.ympev.2010.02.015 20171294

37. Huang S, Tian H, Chen Z, Yu T, Xu A. The evolution of vertebrate tetraspanins: gene loss, retention, and massive positive selection after whole genome duplications. BMC Evol Biol 2010;10:306,2148-10-306. doi: 10.1186/1471-2148-10-306 20939927

38. Gleason RJ, Akintobi AM, Grant BD, Padgett RW. BMP signaling requires retromer-dependent recycling of the type I receptor. Proc Natl Acad Sci U S A 2014;111:2578–83. doi: 10.1073/pnas.1319947111 24550286

39. Greenwald IS, Sternberg PW, Horvitz HR. The lin-12 locus specifies cell fates in Caenorhabditis elegans. Cell 1983;34:435–44. 6616618

40. Foehr ML, Liu J. Dorsoventral patterning of the C. elegans postembryonic mesoderm requires both LIN-12/Notch and TGFbeta signaling. Dev Biol 2008;313:256–66. 18036582

41. Kodoyianni V, Maine EM, Kimble J. Molecular basis of loss-of-function mutations in the glp-1 gene of Caenorhabditis elegans. Mol Biol Cell 1992;3:1199–213. 1457827

42. Obrdlik P, El-Bakkoury M, Hamacher T, Cappellaro C, Vilarino C, Fleischer C, et al. K+ channel interactions detected by a genetic system optimized for systematic studies of membrane protein interactions. Proc Natl Acad Sci U S A 2004;101:12242–7. 15299147

43. Johnsson N, Varshavsky A. Split ubiquitin as a sensor of protein interactions in vivo. Proc Natl Acad Sci U S A 1994;91:10340–4. 7937952

44. Stagljar I, Korostensky C, Johnsson N, te Heesen S. A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo. Proc Natl Acad Sci U S A 1998;95:5187–92. 9560251

45. Watts JL, Morton DG, Bestman J, Kemphues KJ. The C. elegans par-4 gene encodes a putative serine-threonine kinase required for establishing embryonic asymmetry. Development 2000;127:1467–75. 10704392

46. Kim S, Selote DS, Vatamaniuk OK. The N-terminal extension domain of the C. elegans half-molecule ABC transporter, HMT-1, is required for protein-protein interactions and function. PLoS One 2010;5:e12938. doi: 10.1371/journal.pone.0012938 20886084

47. Kurzchalia TV, Ward S. Why do worms need cholesterol? Nat Cell Biol 2003;5:684–8. 12894170

48. Zhu H, Han M. Exploring developmental and physiological functions of Fatty Acid and lipid variants through worm and fly genetics. Annu Rev Genet 2014;48:119–48. doi: 10.1146/annurev-genet-041814-095928 25195508

49. Brenner S. The genetics of Caenorhabditis elegans. Genetics 1974;77:71–94. 4366476

50. Yochem J, Tuck S, Greenwald I, Han M. A gp330/megalin-related protein is required in the major epidermis of Caenorhabditis elegans for completion of molting. Development 1999;126:597–606. 9876188

51. Crowder CM, Westover EJ, Kumar AS, Ostlund RE,Jr, Covey DF. Enantiospecificity of cholesterol function in vivo. J Biol Chem 2001;276:44369–72. 11598105

52. Zhang H, Abraham N, Khan LA, Hall DH, Fleming JT, Gobel V. Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis. Nat Cell Biol 2011;13:1189–201. doi: 10.1038/ncb2328 21926990

53. Marza E, Simonsen KT, Faergeman NJ, Lesa GM. Expression of ceramide glucosyltransferases, which are essential for glycosphingolipid synthesis, is only required in a small subset of C. elegans cells. J Cell Sci 2009;122:822–33. doi: 10.1242/jcs.042754 19240113

54. Nomura KH, Murata D, Hayashi Y, Dejima K, Mizuguchi S, Kage-Nakadai E, et al. Ceramide glucosyltransferase of the nematode Caenorhabditis elegans is involved in oocyte formation and in early embryonic cell division. Glycobiology 2011;21:834–48. doi: 10.1093/glycob/cwr019 21325339

55. Griffitts JS, Whitacre JL, Stevens DE, Aroian RV. Bt toxin resistance from loss of a putative carbohydrate-modifying enzyme. Science 2001;293:860–4. 11486087

56. Griffitts JS, Huffman DL, Whitacre JL, Barrows BD, Marroquin LD, Muller R, et al. Resistance to a bacterial toxin is mediated by removal of a conserved glycosylation pathway required for toxin-host interactions. J Biol Chem 2003;278:45594–602. 12944392

57. Katic I, Vallier LG, Greenwald I. New positive regulators of lin-12 activity in Caenorhabditis elegans include the BRE-5/Brainiac glycosphingolipid biosynthesis enzyme. Genetics 2005;171:1605–15. 16157663

58. Junge HJ, Yang S, Burton JB, et al. TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling. Cell 2009;139:299–311. doi: 10.1016/j.cell.2009.07.048 19837033

59. Ke J, Harikumar KG, Erice C, Chen C, Gu X, Wang L, et al. Structure and function of Norrin in assembly and activation of a Frizzled 4-Lrp5/6 complex. Genes Dev 2013;27:2305–19. doi: 10.1101/gad.228544.113 24186977

60. Berditchevski R. Tetraspanins. Springer 2013;418. Available: http://link.springer.com/book/10.1007%2F978-94-007-6070-7.

61. Dornier E, Coumailleau F, Ottavi JF, Moretti J, Boucheix C, Mauduit P, et al. TspanC8 tetraspanins regulate ADAM10/Kuzbanian trafficking and promote Notch activation in flies and mammals. J Cell Biol 2012;199:481–96. doi: 10.1083/jcb.201201133 23091066

62. Haining EJ, Yang J, Bailey RL, Khan K, Collier R, Tsai S, et al. The TspanC8 subgroup of tetraspanins interacts with A disintegrin and metalloprotease 10 (ADAM10) and regulates its maturation and cell surface expression. J Biol Chem 2012;287:39753–65. doi: 10.1074/jbc.M112.416503 23035126

63. Prox J, Willenbrock M, Weber S, Lehmann T, Schmidt-Arras D, Schwanbeck R, et al. Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10. Cell Mol Life Sci 2012;69:2919–32. doi: 10.1007/s00018-012-0960-2 22446748

64. Sadej R, Grudowska A, Turczyk L, Kordek R, Romanska HM. CD151 in cancer progression and metastasis: a complex scenario. Lab Invest 2014;94:41–51. doi: 10.1038/labinvest.2013.136 24247563

65. Knoblich K, Wang HX, Sharma C, Fletcher AL, Turley SJ, Hemler ME. Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits beta-catenin degradation. Cell Mol Life Sci 2014;71:1305–14. doi: 10.1007/s00018-013-1444-8 23955570

66. Berthier-Vergnes O, Kharbili ME, de la Fouchardiere A, Pointecouteau T, Verrando P, Wierinckx A, et al. Gene expression profiles of human melanoma cells with different invasive potential reveal TSPAN8 as a novel mediator of invasion. Br J Cancer 2011;104:155–65. doi: 10.1038/sj.bjc.6605994 21081927

67. Hemler ME. Tetraspanin proteins promote multiple cancer stages. Nat Rev Cancer 2014;14:49–60. 24505619

68. Padua D, Massague J. Roles of TGFbeta in metastasis. Cell Res 2009;19:89–102. doi: 10.1038/cr.2008.316 19050696

69. Sadej R, Romanska H, Kavanagh D, et al. Tetraspanin CD151 regulates transforming growth factor beta signaling: implication in tumor metastasis. Cancer Res 2010;70:6059–70. doi: 10.1158/0008-5472.CAN-09-3497 20570898

70. Wang HX, Sharma C, Knoblich K, Granter SR, Hemler ME. EWI-2 negatively regulates TGF-beta signaling leading to altered melanoma growth and metastasis. Cell Res 2015;25:370–85. doi: 10.1038/cr.2015.17 25656846

71. Baum PD, Garriga G. Neuronal migrations and axon fasciculation are disrupted in ina-1 integrin mutants. Neuron 1997;19:51–62. 9247263

72. Williams BD, Waterston RH. Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations. J Cell Biol 1994;124:475–90. 8106547

73. Li Y, Wang L, Qiu J, Da L, Tiollais P, Li Z, et al. Human tetraspanin transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein is overexpressed in hepatocellular carcinoma and accelerates tumor cell growth. Acta Biochim Biophys Sin (Shanghai) 2012;44:224–32. doi: 10.1093/abbs/gmr124 22236579

74. Nowee ME, Snijders AM, Rockx DA, de Wit RM, Kosma VM, Hämäläinen K,et al. DNA profiling of primary serous ovarian and fallopian tube carcinomas with array comparative genomic hybridization and multiplex ligation-dependent probe amplification. J Pathol 2007;213:46–55. 17668415

75. Ferrer M, Yunta M, Lazo PA. Pattern of expression of tetraspanin antigen genes in Burkitt lymphoma cell lines. Clin Exp Immunol 1998;113:346–52. 9737661

76. Bankovic J, Stojsic J, Jovanovic D, Andjelkovic T, Milinkovic V, Ruzdijic S, et al. Identification of genes associated with non-small-cell lung cancer promotion and progression. Lung Cancer 2010;67:151–9. doi: 10.1016/j.lungcan.2009.04.010 19473719

77. Gumienny TL, MacNeil LT, Wang H, de Bono M, Wrana JL, Padgett RW. Glypican LON-2 is a conserved negative regulator of BMP-like signaling in Caenorhabditis elegans. Curr Biol 2007;17:159–64. 17240342

78. Savage-Dunn C, Maduzia LL, Zimmerman CM, Roberts AF, Cohen S, Tokarz R, et al. Genetic screen for small body size mutants in C. elegans reveals many TGFbeta pathway components. Genesis 2003;35:239–47. 12717735

79. Hirose T, Nakano Y, Nagamatsu Y, Misumi T, Ohta H, Ohshima Y. Cyclic GMP-dependent protein kinase EGL-4 controls body size and lifespan in C elegans. Development 2003;130:1089–99. 12571101

80. Merris M, Wadsworth WG, Khamrai U, Bittman R, Chitwood DJ, Lenard J. Sterol effects and sites of sterol accumulation in Caenorhabditis elegans: developmental requirement for 4alpha-methyl sterols. J Lipid Res 2003;44:172–81. 12518036

81. Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, et al. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 2003;421:231–7. 12529635

82. Rual JF, Ceron J, Koreth J, Hao T, Nicot AS, Hirozane-Kishikawa T, et al. Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res 2004;14:2162–8. 15489339

83. Wicks SR, Yeh RT, Gish WR, Waterston RH, Plasterk RH. Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map. Nat Genet 2001;28:160–4. 11381264

84. Doitsidou M, Poole RJ, Sarin S, Bigelow H, Hobert O. C. elegans mutant identification with a one-step whole-genome-sequencing and SNP mapping strategy. PLoS One 2010;5:e15435. doi: 10.1371/journal.pone.0015435 21079745

85. Davis MW, Hammarlund M, Harrach T, Hullett P, Olsen S, Jorgensen EM. Rapid single nucleotide polymorphism mapping in C. elegans. BMC Genomics 2005;6:118. 16156901

86. Bigelow H, Doitsidou M, Sarin S, Hobert O. MAQGene: software to facilitate C. elegans mutant genome sequence analysis. Nat Methods 2009;6:549. doi: 10.1038/nmeth.f.260 19620971

87. Sarin S, Bertrand V, Bigelow H, Boyanov A, Doitsidou M, Poole RJ, et al. Analysis of multiple ethyl methanesulfonate-mutagenized Caenorhabditis elegans strains by whole-genome sequencing. Genetics 2010;185:417–30. doi: 10.1534/genetics.110.116319 20439776

88. Homer N, Merriman B, Nelson SF. BFAST: an alignment tool for large scale genome resequencing. PLoS One 2009;4:e7767. doi: 10.1371/journal.pone.0007767 19907642

89. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009;25:2078–9. doi: 10.1093/bioinformatics/btp352 19505943

90. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010;38:e164. doi: 10.1093/nar/gkq603 20601685

91. Dickinson DJ, Ward JD, Reiner DJ, Goldstein B. Engineering the Caenorhabditis elegans genome using Cas9-triggered homologous recombination. Nat Methods 2013;10:1028–34. doi: 10.1038/nmeth.2641 23995389

92. Friedland AE, Tzur YB, Esvelt KM, Colaiacovo MP, Church GM, Calarco JA. Heritable genome editing in C. elegans via a CRISPR-Cas9 system. Nat Methods 2013;10:741–3. doi: 10.1038/nmeth.2532 23817069

93. Frokjaer-Jensen C, Davis MW, Hopkins CE, Newman BJ, Thummel JM, Olesen SP, et al. Single-copy insertion of transgenes in Caenorhabditis elegans. Nat Genet 2008;40:1375–83. doi: 10.1038/ng.248 18953339

94. Eddy SR. A new generation of homology search tools based on probabilistic inference. Genome Inform 2009;23:205–11. 20180275

95. Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, et al. Pfam: the protein families database. Nucleic Acids Res 2014;42:D222–30. doi: 10.1093/nar/gkt1223 24288371

96. Sonnhammer EL, Gabaldon T, Sousa da Silva AW, Martin M, Robinson-Rechavi M, Boeckmann B, et al. Big data and other challenges in the quest for orthologs. Bioinformatics 2014;30:2993–8. doi: 10.1093/bioinformatics/btu492 25064571

97. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 2013;30:772–80. doi: 10.1093/molbev/mst010 23329690

98. Capella-Gutierrez S, Silla-Martinez JM, Gabaldon T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 2009;25:1972–3. doi: 10.1093/bioinformatics/btp348 19505945

99. Criscuolo A, Gribaldo S. BMGE (Block Mapping and Gathering with Entropy): a new software for selection of phylogenetic informative regions from multiple sequence alignments. BMC Evol Biol 2010;10:210,2148-10-210. doi: 10.1186/1471-2148-10-210 20626897

100. Whelan S, Goldman N. A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol Biol Evol 2001;18:691–9. 11319253

101. Price MN, Dehal PS, Arkin AP. FastTree 2—approximately maximum-likelihood trees for large alignments. PLoS One 2010;5:e9490. doi: 10.1371/journal.pone.0009490 20224823

102. Price MN, Dehal PS, Arkin AP. FastTree: computing large minimum evolution trees with profiles instead of a distance matrix. Mol Biol Evol 2009;26:1641–50. doi: 10.1093/molbev/msp077 19377059

103. Grefen C, Lalonde S, Obrdlik P. Split-ubiquitin system for identifying protein-protein interactions in membrane and full-length proteins. Curr Protoc Neurosci 2007;Chapter 5:Unit 5.27.

104. Larkin MA, Blackshields G, Brown NP, et al. Clustal W and Clustal X version 2.0. Bioinformatics 2007;23:2947–8. 17846036

105. Moribe H, Yochem J, Yamada H, Tabuse Y, Fujimoto T, Mekada E. Tetraspanin protein (TSP-15) is required for epidermal integrity in caenorhabditis elegans. J Cell Sci 2004;117(Pt 22): 5209–5220. 15454573

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 5
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#