Clustering and Negative Feedback by Endocytosis in Planar Cell Polarity Signaling Is Modulated by Ubiquitinylation of Prickle

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Many epithelial cells display a level of organization in which cellular structures or appendages are positioned asymmetrically within the cell along an axis perpendicular to the apical-basal axis of the cell. When the direction of this polarization is coordinated within the plane of the epithelium, this phenomenon is referred to as planar cell polarity (PCP). PCP is organized, at least in part, by a group of molecules that interact across cell-cell junctions and segregate into two groups that localize on opposite sides of each cell. Their asymmetric localization is thought to both produce molecular asymmetry, and to mark polarized domains within the cell for subsequent morphological polarization. In segregating to produce molecular asymmetry, these proteins participate in both positive and negative feedback, much like ferromagnets, to align their localization within and between neighboring cells. In this work, we identify a mechanism for negative feedback that utilizes the protein Prickle, one of the PCP signaling components. Levels of Prickle are precisely regulated, in part by a ubiquitinylation mechanism that targets excess protein for degradation. Prickle mediates internalization and removal of one class of PCP proteins, thereby causing repulsion of opposite ‘poles.’ Excess Prickle disrupts this mechanism and interferes with establishing polarity.

Vyšlo v časopise: Clustering and Negative Feedback by Endocytosis in Planar Cell Polarity Signaling Is Modulated by Ubiquitinylation of Prickle. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005259
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005259

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1. Wong LL, Adler PN (1993) Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing hairs. Journal of Cell Biology 123 : 209–221. 8408199

2. Vladar EK, Antic D, Axelrod JD (2009) Planar cell polarity signaling: The developing cell's compass. Cold Spring Harb Perspect Biol 1: a002964 235–253. doi: 10.1101/cshperspect.a002964 20066108

3. Wallingford JB (2012) Planar cell polarity and the developmental control of cell behavior in vertebrate embryos. Annu Rev Cell Dev Biol 28 : 627–653. doi: 10.1146/annurev-cellbio-092910-154208 22905955

4. Tree DR, Ma D, Axelrod JD (2002) A three-tiered mechanism for regulation of planar cell polarity. Semin Cell Dev Biol 13 : 217–224. 12137730

5. Vinson CR, Adler PN (1987) Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila. Nature 329 : 549–551. 3116434

6. Vinson CR, Conover S, Adler PN (1989) A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains. Nature 338 : 263–264. 2493583

7. Klingensmith J, Nusse R, Perrimon N (1994) The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. Genes and Development 8 : 118–130. 8288125

8. Thiesen H, Purcell J, Bennett M, Kansagara D, Syed A, et al. (1994) dishevelled is required during wingless signaling to establish both cell polarity and cell identity. Development 120 : 347–360. 8149913

9. Feiguin F, Hannus M, Mlodzik M, Eaton S (2001) The ankyrin repeat protein Diego mediates Frizzled-dependent planar polarization. Dev Cell 1 : 93–101. 11703927

10. Taylor J, Abramova N, Charlton J, Adler PN (1998) Van Gogh: a new Drosophila tissue polarity gene. Genetics 150 : 199–210. 9725839

11. Wolff T, Rubin GM (1998) Strabismus, a novel gene that regulates tissue polarity and cell fate decisions in Drosophila. Development 125 : 1149–1159. 9463361

12. Gubb D, Green C, Huen D, Coulson D, Johnson G, et al. (1999) The balance between isoforms of the prickle LIM domain protein is critical for planar polarity in Drosophila imaginal discs. Genes Dev 13 : 2315–2327. 10485852

13. Chae J, Kim MJ, Goo JH, Collier S, Gubb D, et al. (1999) The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family. Development 126 : 5421–5429. 10556066

14. Usui T, Shima Y, Shimada Y, Hirano S, Burgess RW, et al. (1999) Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 98 : 585–595. 10490098

15. Chin ML, Mlodzik M (2013) The Drosophila selectin furrowed mediates intercellular planar cell polarity interactions via frizzled stabilization. Dev Cell 26 : 455–468. doi: 10.1016/j.devcel.2013.07.006 23973164

16. Hermle T, Guida MC, Beck S, Helmstadter S, Simons M (2013) Drosophila ATP6AP2/VhaPRR functions both as a novel planar cell polarity core protein and a regulator of endosomal trafficking. EMBO J 32 : 245–259. doi: 10.1038/emboj.2012.323 23292348

17. Strutt H, Strutt D (2009) Asymmetric localisation of planar polarity proteins: Mechanisms and consequences. Semin Cell Dev Biol 20 : 957–963. doi: 10.1016/j.semcdb.2009.03.006 19751618

18. Amonlirdviman K, Khare NA, Tree DR, Chen WS, Axelrod JD, et al. (2005) Mathematical modeling of planar cell polarity to understand domineering nonautonomy. Science 307 : 423–426. 15662015

19. Tree DR, Shulman JM, Rousset R, Scott MP, Gubb D, et al. (2002) Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell 109 : 371–381. 12015986

20. Adler PN, Taylor J, Charlton J (2000) The domineering non-autonomy of frizzled and van Gogh clones in the Drosophila wing is a consequence of a disruption in local signaling. Mech Dev 96 : 197–207. 10960784

21. Gubb D, Garcia-Bellido A (1982) A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. J Embryol Exp Morphol 68 : 37–57. 6809878

22. Axelrod JD, Tomlin CJ (2011) Modeling the control of planar cell polarity. Wiley Interdiscip Rev Syst Biol Med 3 : 588–605. doi: 10.1002/wsbm.138 21755606

23. Matis M, Axelrod JD (2013) Regulation of PCP by the Fat signaling pathway. Genes Dev 27 : 2207–2220. doi: 10.1101/gad.228098.113 24142873

24. Wu J, Roman AC, Carvajal-Gonzalez JM, Mlodzik M (2013) Wg and Wnt4 provide long-range directional input to planar cell polarity orientation in Drosophila. Nat Cell Biol 15 : 1045–1055. doi: 10.1038/ncb2806 23912125

25. Sagner A, Merkel M, Aigouy B, Gaebel J, Brankatschk M, et al. (2012) Establishment of Global Patterns of Planar Polarity during Growth of the Drosophila Wing Epithelium. Curr Biol 22 : 1296–1301. doi: 10.1016/j.cub.2012.04.066 22727699

26. Harumoto T, Ito M, Shimada Y, Kobayashi TJ, Ueda HR, et al. (2010) Atypical cadherins dachsous and fat control dynamics of noncentrosomal microtubules in planar cell polarity. Dev Cell 19 : 389–401. doi: 10.1016/j.devcel.2010.08.004 20817616

27. Olofsson J, Sharp KA, Matis M, Cho B, Axelrod JD (2014) Prickle/Spiny-legs isoforms control the polarity of the apical microtubule network in PCP. Development (in press).

28. Shimada Y, Yonemura S, Ohkura H, Strutt D, Uemura T (2006) Polarized Transport of Frizzled along the Planar Microtubule Arrays in Drosophila Wing Epithelium. Dev Cell 10 : 209–222. 16459300

29. Meinhardt H (2007) Computational modelling of epithelial patterning. Curr Opin Genet Dev 17 : 272–280. 17627806

30. Chen WS, Antic D, Matis M, Logan CY, Povelones M, et al. (2008) Asymmetric homotypic interactions of the atypical cadherin flamingo mediate intercellular polarity signaling. Cell 133 : 1093–1105. doi: 10.1016/j.cell.2008.04.048 18555784

31. Wu J, Mlodzik M (2008) The frizzled extracellular domain is a ligand for Van Gogh/Stbm during nonautonomous planar cell polarity signaling. Dev Cell 15 : 462–469. doi: 10.1016/j.devcel.2008.08.004 18804440

32. Strutt H, Warrington SJ, Strutt D (2011) Dynamics of core planar polarity protein turnover and stable assembly into discrete membrane subdomains. Dev Cell 20 : 511–525. doi: 10.1016/j.devcel.2011.03.018 21497763

33. Bastock R, Strutt H, Strutt D (2003) Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development 130 : 3007–3014. 12756182

34. d'Azzo A, Bongiovanni A, Nastasi T (2005) E3 ubiquitin ligases as regulators of membrane protein trafficking and degradation. Traffic 6 : 429–441. 15882441

35. Hershko A, Ciechanover A, Varshavsky A (2000) Basic Medical Research Award. The ubiquitin system. Nat Med 6 : 1073–1081. 11017125

36. Narimatsu M, Bose R, Pye M, Zhang L, Miller B, et al. (2009) Regulation of planar cell polarity by Smurf ubiquitin ligases. Cell 137 : 295–307. doi: 10.1016/j.cell.2009.02.025 19379695

37. Strutt H, Searle E, Thomas-Macarthur V, Brookfield R, Strutt D (2013) A Cul-3-BTB ubiquitylation pathway regulates junctional levels and asymmetry of core planar polarity proteins. Development 140 : 1693–1702. doi: 10.1242/dev.089656 23487316

38. Strutt H, Thomas-MacArthur V, Strutt D (2013) Strabismus promotes recruitment and degradation of farnesylated prickle in Drosophila melanogaster planar polarity specification. PLoS Genet 9: e1003654. doi: 10.1371/journal.pgen.1003654 23874239

39. Mummery-Widmer JL, Yamazaki M, Stoeger T, Novatchkova M, Bhalerao S, et al. (2009) Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi. Nature 458 : 987–992. doi: 10.1038/nature07936 19363474

40. Jiang J, Struhl G (1998) Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb. Nature 391 : 493–496. 9461217

41. Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6 : 369–381. 16633365

42. Cardozo T, Pagano M (2004) The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol 5 : 739–751. 15340381

43. Morais-de-Sa E, Mukherjee A, Lowe N, St Johnston D (2014) Slmb antagonises the aPKC/Par-6 complex to control oocyte and epithelial polarity. Development 141 : 2984–2992. doi: 10.1242/dev.109827 25053432

44. Skwarek LC, Windler SL, de Vreede G, Rogers GC, Bilder D (2014) The F-box protein Slmb restricts the activity of aPKC to polarize epithelial cells. Development 141 : 2978–2983. doi: 10.1242/dev.109694 25053431

45. Adler PN, Liu J, Charlton J (2000) Cell size and the morphogenesis of wing hairs in Drosophila. Genesis 28 : 82–91. 11064425

46. Weigmann K, Cohen SM, Lehner CF (1997) Cell cycle progression, growth and patterning in imaginal discs despite inhibition of cell division after inactivation of Drosophila Cdc2 kinase. Development 124 : 3555–3563. 9342048

47. Strutt H, Strutt D (2008) Differential stability of flamingo protein complexes underlies the establishment of planar polarity. Curr Biol 18 : 1555–1564. doi: 10.1016/j.cub.2008.08.063 18804371

48. Li Y, Gazdoiu S, Pan ZQ, Fuchs SY (2004) Stability of homologue of Slimb F-box protein is regulated by availability of its substrate. J Biol Chem 279 : 11074–11080. 14707120

49. Zhou P, Howley PM (1998) Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases. Mol Cell 2 : 571–580. 9844630

50. Paemka L, Mahajan VB, Ehaideb SN, Skeie JM, Tan MC, et al. (2015) Seizures Are Regulated by Ubiquitin-specific Peptidase 9 X-linked (USP9X), a De-Ubiquitinase. PLoS Genet 11: e1005022. doi: 10.1371/journal.pgen.1005022 25763846

51. Classen A-K, Anderson KI, Marois E, Eaton S (2005) Hexagonal packing of Drosophila wing epithelial cells by the planar cell polarity pathway. Dev Cell 9 : 805–817. 16326392

52. Jenny A, Darken RS, Wilson PA, Mlodzik M (2003) Prickle and Strabismus form a functional complex to generate a correct axis during planar cell polarity signaling. EMBO J 22 : 4409–4420. 12941693

53. Das G, Jenny A, Klein TJ, Eaton S, Mlodzik M (2004) Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes. Development 131 : 4467–4476. 15306567

54. Jenny A, Reynolds-Kenneally J, Das G, Burnett M, Mlodzik M (2005) Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled binding. Nat Cell Biol 7 : 691–697. 15937478

55. Aigouy B, Farhadifar R, Staple DB, Sagner A, Roper JC, et al. (2010) Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila. Cell 142 : 773–786. doi: 10.1016/j.cell.2010.07.042 20813263

56. Venken KJ, He Y, Hoskins RA, Bellen HJ (2006) P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 314 : 1747–1751. 17138868

57. Bischof J, Maeda RK, Hediger M, Karch F, Basler K (2007) An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases. Proc Natl Acad Sci U S A 104 : 3312–3317. 17360644

58. Classen AK, Aigouy B, Giangrande A, Eaton S (2008) Imaging Drosophila pupal wing morphogenesis. Methods Mol Biol 420 : 265–275. doi: 10.1007/978-1-59745-583-1_16 18641953

59. Choo YS, Zhang Z (2009) Detection of protein ubiquitination. J Vis Exp.