Exocyst-mediated apical Wg secretion activates signaling in the Drosophila wing epithelium


Autoři: Varun Chaudhary aff001;  Michael Boutros aff001
Působiště autorů: German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics and Heidelberg University, Department of Cell and Molecular Biology, Im Neuenheimer Feld, Heidelberg, Germany aff001
Vyšlo v časopise: Exocyst-mediated apical Wg secretion activates signaling in the Drosophila wing epithelium. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008351
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008351

Souhrn

Wnt proteins are secreted signaling factors that regulate cell fate specification and patterning decisions throughout the animal kingdom. In the Drosophila wing epithelium, Wingless (Wg, the homolog of Wnt1) is secreted from a narrow strip of cells at the dorsal-ventral boundary. However, the route of Wg secretion in polarized epithelial cells remains poorly understood and key proteins involved in this process are still unknown. Here, we performed an in vivo RNAi screen and identified members of the exocyst complex to be required for apical but not basolateral Wg secretion. Specifically blocking the apical Wg secretion leads to reduced downstream signaling. Using an in vivo ‘temporal-rescue’ assay, our results further indicate that apically secreted Wg activates target genes that require high signaling activity. In conclusion, our results demonstrate that the exocyst is required for an apical route of Wg secretion from polarized wing epithelial cells.

Klíčová slova:

Biology and life sciences – Physiology – Physiological processes – Secretion – Genetics – Epigenetics – RNA interference – Gene expression – Genetic interference – Biochemistry – Nucleic acids – RNA – Proteins – Protein transport – Protein secretion – Cell biology – Signal transduction – Cell signaling – Signaling cascades – Wnt signaling cascade – Cell processes – Cellular types – Animal cells – Epithelial cells – Anatomy – Biological tissue – Epithelium – Molecular biology – Molecular biology techniques – Cloning – Organisms – Eukaryota – Animals – Invertebrates – Arthropoda – Insects – Drosophila – Drosophila melanogaster – Medicine and health sciences – Research and analysis methods – Animal studies – Experimental organism systems – Model organisms – Animal models


Zdroje

1. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20: 781–810. doi: 10.1146/annurev.cellbio.20.010403.113126 15473860

2. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17: 9–26. doi: 10.1016/j.devcel.2009.06.016 19619488

3. Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36: 1461–1473. doi: 10.1038/onc.2016.304 27617575

4. Sharma RP. Wingless, a new mutant in D. melanogaster. Drosoph Inf Serv. 1973;50: 134.

5. Sharma RP, Chopra VL. Effect of the wingless (wg1) mutation on wing and haltere development in Drosophila melanogaster. Dev Biol. 1976;48: 461–465. doi: 10.1016/0012-1606(76)90108-1 815114

6. Niehrs C. The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol. 2012;13: 767–779. doi: 10.1038/nrm3470 23151663

7. van Amerongen R, Mikels A, Nusse R. Alternative wnt signaling is initiated by distinct receptors. Sci Signal. 2008;1: re9. doi: 10.1126/scisignal.135re9 18765832

8. van den Heuvel M, Harryman-Samos C, Klingensmith J, Perrimon N, Nusse R. Mutations in the segment polarity genes wingless and porcupine impair secretion of the wingless protein. EMBO J. 1993;12: 5293–5302. 8262072

9. Bänziger C, Soldini D, Schütt C, Zipperlen P, Hausmann G, Basler K. Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell. 2006;125: 509–522. doi: 10.1016/j.cell.2006.02.049 16678095

10. Bartscherer K, Pelte N, Ingelfinger D, Boutros M. Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell. 2006;125: 523–533. doi: 10.1016/j.cell.2006.04.009 16678096

11. Goodman RM, Thombre S, Firtina Z, Gray D, Betts D, Roebuck J, et al. Sprinter: a novel transmembrane protein required for Wg secretion and signaling. Development. 2006;133: 4901–4911. doi: 10.1242/dev.02674 17108000

12. Buechling T, Chaudhary V, Spirohn K, Weiss M, Boutros M. p24 proteins are required for secretion of Wnt ligands. EMBO Rep. EMBO Press; 2011;12: 1265–1272.

13. Port F, Hausmann G, Basler K. A genome-wide RNA interference screen uncovers two p24 proteins as regulators of Wingless secretion. EMBO Rep. 2011;12: 1144–1152. doi: 10.1038/embor.2011.165 21886182

14. Coudreuse DYM, Roël G, Betist MC, Destrée O, Korswagen HC. Wnt gradient formation requires retromer function in Wnt-producing cells. Science. 2006;312: 921–924. doi: 10.1126/science.1124856 16645052

15. Belenkaya TY, Wu Y, Tang X, Zhou B, Cheng L, Sharma YV, et al. The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network. Dev Cell. 2008;14: 120–131. doi: 10.1016/j.devcel.2007.12.003 18160348

16. Franch-Marro X, Wendler F, Guidato S, Griffith J, Baena-Lopez A, Itasaki N, et al. Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex. Nat Cell Biol. 2008;10: 170–177. doi: 10.1038/ncb1678 18193037

17. Pan C-L, Baum PD, Gu M, Jorgensen EM, Clark SG, Garriga G. C. elegans AP-2 and retromer control Wnt signaling by regulating mig-14/Wntless. Dev Cell. 2008;14: 132–139. doi: 10.1016/j.devcel.2007.12.001 18160346

18. Port F, Kuster M, Herr P, Furger E, Bänziger C, Hausmann G, et al. Wingless secretion promotes and requires retromer-dependent cycling of Wntless. Nat Cell Biol. 2008;10: 178–185. doi: 10.1038/ncb1687 18193032

19. Yang P-T, Lorenowicz MJ, Silhankova M, Coudreuse DYM, Betist MC, Korswagen HC. Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells. Dev Cell. 2008;14: 140–147. doi: 10.1016/j.devcel.2007.12.004 18160347

20. Glaeser K, Urban M, Fenech E, Voloshanenko O, Kranz D, Lari F, et al. ERAD-dependent control of the Wnt secretory factor Evi. EMBO J. 2018;37. doi: 10.15252/embj.201797311 29378775

21. Yu J, Chia J, Canning CA, Jones CM, Bard FA, Virshup DM. WLS retrograde transport to the endoplasmic reticulum during Wnt secretion. Dev Cell. 2014;29: 277–291. doi: 10.1016/j.devcel.2014.03.016 24768165

22. Fristrom DK, Fristrom JW. The metamorphic development of the adult epidermis. In: Bate M, A MA, editors. The development of Drosophila melanogaster. Cold Spring Harbor Press; 1993. pp. 843–897.

23. González F, Swales L, Bejsovec A, Skaer H, Martinez Arias A. Secretion and movement of wingless protein in the epidermis of the Drosophila embryo. Mech Dev. 1991;35: 43–54. doi: 10.1016/0925-4773(91)90040-d 1720017

24. Simmonds AJ, dosSantos G, Livne-Bar I, Krause HM. Apical Localization of wingless Transcripts Is Required for Wingless Signaling. Cell. 2001;105: 197–207. doi: 10.1016/s0092-8674(01)00311-7 11336670

25. Strigini M, Cohen SM. Wingless gradient formation in the Drosophila wing. Curr Biol. 2000;10: 293–300. doi: 10.1016/s0960-9822(00)00378-x 10744972

26. Gallet A, Staccini-Lavenant L, Thérond PP. Cellular trafficking of the glypican Dally-like is required for full-strength Hedgehog signaling and wingless transcytosis. Dev Cell. 2008;14: 712–725. doi: 10.1016/j.devcel.2008.03.001 18477454

27. Marois E, Mahmoud A, Eaton S. The endocytic pathway and formation of the Wingless morphogen gradient. Development. The Company of Biologists Ltd; 2006;133: 307–317. doi: 10.1242/dev.02197 16354714

28. Yamazaki Y, Palmer L, Alexandre C, Kakugawa S, Beckett K, Gaugue I, et al. Godzilla-dependent transcytosis promotes Wingless signalling in Drosophila wing imaginal discs. Nat Cell Biol. 2016;18: 451–457. doi: 10.1038/ncb3325 26974662

29. Hemalatha A, Prabhakara C, Mayor S. Endocytosis of Wingless via a dynamin-independent pathway is necessary for signaling in Drosophila wing discs. Proc Natl Acad Sci U S A. National Academy of Sciences; 2016;113: E6993–E7002. doi: 10.1073/pnas.1610565113 27791132

30. Pfeiffer S, Ricardo S, Manneville J-B, Alexandre C, Vincent J-P. Producing Cells Retain and Recycle Wingless in Drosophila Embryos. Curr Biol. 2002;12: 957–962. doi: 10.1016/s0960-9822(02)00867-9 12062063

31. Heider MR, Munson M. Exorcising the exocyst complex. Traffic. 2012;13: 898–907. doi: 10.1111/j.1600-0854.2012.01353.x 22420621

32. Hertzog M, Chavrier P. Cell polarity during motile processes: keeping on track with the exocyst complex. Biochem J. 2011;433: 403–409. doi: 10.1042/BJ20101214 21235523

33. Liu J, Guo W. The exocyst complex in exocytosis and cell migration. Protoplasma. 2012;249: 587–597. doi: 10.1007/s00709-011-0330-1 21997494

34. Murthy M, Ranjan R, Denef N, Higashi MEL, Schupbach T, Schwarz TL. Sec6 mutations and the Drosophila exocyst complex. J Cell Sci. 2005;118: 1139–1150. doi: 10.1242/jcs.01644 15728258

35. Beronja S, Laprise P, Papoulas O, Pellikka M, Sisson J, Tepass U. Essential function of Drosophila Sec6 in apical exocytosis of epithelial photoreceptor cells. J Cell Biol. 2005;169: 635–646. doi: 10.1083/jcb.200410081 15897260

36. Murthy M, Teodoro RO, Miller TP, Schwarz TL. Sec5, a member of the exocyst complex, mediates Drosophila embryo cellularization. Development. 2010;137: 2773–2783. doi: 10.1242/dev.048330 20630948

37. Phillips RG, Whittle JR. wingless expression mediates determination of peripheral nervous system elements in late stages of Drosophila wing disc development. Development. 1993;118: 427–438. 8223270

38. Nolo R, Abbott LA, Bellen HJ. Senseless, a Zn Finger Transcription Factor, Is Necessary and Sufficient for Sensory Organ Development in Drosophila. Cell. 2000;102: 349–362. doi: 10.1016/s0092-8674(00)00040-4 10975525

39. Jafar-Nejad H, Tien A-C, Acar M, Bellen HJ. Senseless and Daughterless confer neuronal identity to epithelial cells in the Drosophila wing margin. Development. 2006;133: 1683–1692. doi: 10.1242/dev.02338 16554363

40. Couso JP, Bishop SA, Martinez Arias A. The wingless signalling pathway and the patterning of the wing margin in Drosophila. Development. 1994;120: 621–636. 8162860

41. Zecca M, Basler K, Struhl G. Direct and Long-Range Action of a Wingless Morphogen Gradient. Cell. 1996;87: 833–844. doi: 10.1016/s0092-8674(00)81991-1 8945511

42. Carroll SB, Gates J, Keys DN, Paddock SW, Panganiban GE, Selegue JE, et al. Pattern formation and eyespot determination in butterfly wings. Science. 1994;265: 109–114. doi: 10.1126/science.7912449 7912449

43. Diaz-Benjumea FJ, Cohen SM. Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. Development. 1995;121: 4215–4225. 8575321

44. Chaudhary V, Hingole S, Frei J, Port F, Strutt D, Boutros M. Robust Wnt signaling is maintained by a Wg protein gradient and Fz2 receptor activity in the developing Drosophila wing. Development. 2019;146. doi: 10.1242/dev.174789 31399474

45. Cadigan KM, Fish MP, Rulifson EJ, Nusse R. Wingless Repression of Drosophila frizzled 2 Expression Shapes the Wingless Morphogen Gradient in the Wing. Cell. 1998;93: 767–777. doi: 10.1016/s0092-8674(00)81438-5 9630221

46. Neumann CJ, Cohen SM. Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. Development. 1997;124: 871–880. 9043068

47. Struhl G, Basler K. Organizing activity of wingless protein in Drosophila. Cell. 1993;72: 527–540. doi: 10.1016/0092-8674(93)90072-x 8440019

48. Alexandre C, Baena-Lopez A, Vincent J-P. Patterning and growth control by membrane-tethered Wingless. Nature. 2014;505: 180–185. doi: 10.1038/nature12879 24390349

49. Yamazaki Y, Schönherr C, Varshney GK, Dogru M, Hallberg B, Palmer RH. Goliath family E3 ligases regulate the recycling endosome pathway via VAMP3 ubiquitylation. EMBO J. 2013;32: 524–537. doi: 10.1038/emboj.2013.1 23353890

50. Shin DM, Zhao XS, Zeng W, Mozhayeva M, Muallem S. The mammalian Sec6/8 complex interacts with Ca(2+) signaling complexes and regulates their activity. J Cell Biol. 2000;150: 1101–1112. doi: 10.1083/jcb.150.5.1101 10973998

51. Yamamoto H, Sato A, Kikuchi A. Apical secretion of Wnt1 in polarized epithelial cells is regulated by exocyst-mediated trafficking. J Biochem. 2017;162: 317–326. doi: 10.1093/jb/mvx035 28992081

52. Wu J, Klein TJ, Mlodzik M. Subcellular localization of frizzled receptors, mediated by their cytoplasmic tails, regulates signaling pathway specificity. PLoS Biol. 2004;2: E158. doi: 10.1371/journal.pbio.0020158 15252441

53. Strutt DI. Asymmetric Localization of Frizzled and the Establishment of Cell Polarity in the Drosophila Wing. Mol Cell. 2001;7: 367–375. 11239465

54. Seto ES, Bellen HJ. Internalization is required for proper Wingless signaling in Drosophila melanogaster. J Cell Biol. 2006;173: 95–106. doi: 10.1083/jcb.200510123 16606693

55. Beckett K, Monier S, Palmer L, Alexandre C, Green H, Bonneil E, et al. Drosophila S2 cells secrete wingless on exosome-like vesicles but the wingless gradient forms independently of exosomes. Traffic. 2013;14: 82–96. doi: 10.1111/tra.12016 23035643

56. Greco V, Hannus M, Eaton S. Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell. 2001;106: 633–645. doi: 10.1016/s0092-8674(01)00484-6 11551510

57. Gross JC, Chaudhary V, Bartscherer K, Boutros M. Active Wnt proteins are secreted on exosomes. Nat Cell Biol. 2012;14: 1036–1045. doi: 10.1038/ncb2574 22983114

58. Korkut C, Ataman B, Ramachandran P, Ashley J, Barria R, Gherbesi N, et al. Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell. 2009;139: 393–404. doi: 10.1016/j.cell.2009.07.051 19837038

59. Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, Inanlou MR, Chiu E, et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell. 2012;151: 1542–1556. doi: 10.1016/j.cell.2012.11.024 23260141

60. Neumann S, Coudreuse DYM, van der Westhuyzen DR, Eckhardt ERM, Korswagen HC, Schmitz G, et al. Mammalian Wnt3a is released on lipoprotein particles. Traffic. 2009;10: 334–343. doi: 10.1111/j.1600-0854.2008.00872.x 19207483

61. Panáková D, Sprong H, Marois E, Thiele C, Eaton S. Lipoprotein particles are required for Hedgehog and Wingless signalling. Nature. 2005;435: 58–65. doi: 10.1038/nature03504 15875013

62. Mulligan KA, Fuerer C, Ching W, Fish M, Willert K, Nusse R. Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility. Proc Natl Acad Sci U S A. 2012;109: 370–377. doi: 10.1073/pnas.1119197109 22203956

63. Montagne J, Stewart MJ, Stocker H, Hafen E, Kozma SC, Thomas G. Drosophila S6 kinase: a regulator of cell size. Science. 1999;285: 2126–2129. doi: 10.1126/science.285.5436.2126 10497130

64. Thompson BJ, Cohen SM. The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila. Cell. 2006;126: 767–774. doi: 10.1016/j.cell.2006.07.013 16923395

65. Kassis JA, Noll E, VanSickle EP, Odenwald WF, Perrimon N. Altering the insertional specificity of a Drosophila transposable element. Proc Natl Acad Sci U S A. National Academy of Sciences; 1992;89: 1919–1923. doi: 10.1073/pnas.89.5.1919 1311855

66. Dietzl G, Chen D, Schnorrer F, Su K-C, Barinova Y, Fellner M, et al. A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature. 2007;448: 151–156. doi: 10.1038/nature05954 17625558

67. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9: 671–675. doi: 10.1038/nmeth.2089 22930834

68. Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH, Friman O, et al. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol. 2006;7: R100. doi: 10.1186/gb-2006-7-10-r100 17076895

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