Strabismus Promotes Recruitment and Degradation of Farnesylated Prickle in Planar Polarity Specification
The core planar polarity proteins are required to specify the orientation of structures that are polarised in the plane of the epithelium. In the Drosophila melanogaster wing, the core proteins localise asymmetrically at either proximal or distal cell edges. Asymmetric localisation is thought to be biased by long-range cues, causing asymmetric complexes to become aligned with the tissue axes. Core proteins are then thought to participate in feedback interactions that are necessary to amplify asymmetry, and in order for such feedback interactions to operate correctly, the levels of the core proteins at junctions must be tightly regulated. We have investigated regulation of the core protein Prickle (Pk) in the pupal wing. The core protein Strabismus (Stbm) is required to recruit Pk into asymmetric complexes at proximal cell ends, and we report here that it also promotes proteasomal degradation of excess Pk, probably via a Cullin-1 dependent process. We also show for the first time that Pk is farnesylated in vivo, and this is essential for Pk function in the wing. Notably, farnesylation of Pk is necessary for it to be recruited into asymmetric complexes and function in feedback amplification, probably by reinforcing weak direct interactions between Stbm and Pk. Furthermore, farnesylation is also required for Stbm to promote proteasomal degradation of Pk. We propose that Stbm recruits farnesylated Pk into asymmetric complexes, but also promotes degradation of excess Pk that would otherwise perturb feedback amplification.
Vyšlo v časopise:
Strabismus Promotes Recruitment and Degradation of Farnesylated Prickle in Planar Polarity Specification. PLoS Genet 9(7): e32767. doi:10.1371/journal.pgen.1003654
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003654
Souhrn
The core planar polarity proteins are required to specify the orientation of structures that are polarised in the plane of the epithelium. In the Drosophila melanogaster wing, the core proteins localise asymmetrically at either proximal or distal cell edges. Asymmetric localisation is thought to be biased by long-range cues, causing asymmetric complexes to become aligned with the tissue axes. Core proteins are then thought to participate in feedback interactions that are necessary to amplify asymmetry, and in order for such feedback interactions to operate correctly, the levels of the core proteins at junctions must be tightly regulated. We have investigated regulation of the core protein Prickle (Pk) in the pupal wing. The core protein Strabismus (Stbm) is required to recruit Pk into asymmetric complexes at proximal cell ends, and we report here that it also promotes proteasomal degradation of excess Pk, probably via a Cullin-1 dependent process. We also show for the first time that Pk is farnesylated in vivo, and this is essential for Pk function in the wing. Notably, farnesylation of Pk is necessary for it to be recruited into asymmetric complexes and function in feedback amplification, probably by reinforcing weak direct interactions between Stbm and Pk. Furthermore, farnesylation is also required for Stbm to promote proteasomal degradation of Pk. We propose that Stbm recruits farnesylated Pk into asymmetric complexes, but also promotes degradation of excess Pk that would otherwise perturb feedback amplification.
Zdroje
1. StruttH, StruttD (2009) Asymmetric localisation of planar polarity proteins: Mechanisms and consequences. Semin Cell Dev Biol 20: 957–963.
2. McNeillH (2010) Planar cell polarity: keeping hairs straight is not so simple. Cold Spring Harb Perspect Biol 2: a003376.
3. AdlerPN (2012) The frizzled/stan pathway and planar cell polarity in the Drosophila wing. Curr Top Dev Biol 101: 1–31.
4. StruttH, WarringtonSJ, StruttD (2011) Dynamics of core planar polarity protein turnover and stable assembly into discrete membrane subdomains. Dev Cell 20: 511–525.
5. TreeDRP, ShulmanJM, RoussetR, ScottMP, GubbD, et al. (2002) Prickle mediates feedback amplification to generate asymmetric planar cell polarity signalling. Cell 109: 371–381.
6. JennyA, DarkenRS, WilsonPA, MlodzikM (2003) Prickle and Strabismus form a functional complex to generate a correct axis during planar cell polarity signaling. EMBO J 22: 4409–4420.
7. AmonlirdvimanK, KhareNA, TreeDRP, ChenW-S, AxelrodJD, et al. (2005) Mathematical modeling of planar cell polarity to understand domineering non-autonomy. Science 307: 423–426.
8. Le GarrecJF, LopezP, KerszbergM (2006) Establishment and maintenance of planar epithelial cell polarity by asymmetric cadherin bridges: a computer model. Dev Dyn 235: 235–246.
9. BurakY, ShraimanBI (2009) Order and stochastic dynamics in Drosophila planar cell polarity. PLoS Comput Biol 5: e1000628.
10. AxelrodJD (2009) Progress and challenges in understanding planar cell polarity signaling. Semin Cell Dev Biol 20: 964–971.
11. BlairSS (2012) Cell polarity: overdosing on PCPs. Curr Biol 22: R567–569.
12. ThomasC, StruttD (2012) The roles of the cadherins Fat and Dachsous in planar polarity specification in Drosophila. Dev Dyn 241: 27–39.
13. GubbD, GreenC, HuenD, CoulsonD, JohnsonG, 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.
14. GubbD, García-BellidoA (1982) A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. J Embryol Exp Morphol 68: 37–57.
15. WongLL, AdlerPN (1993) Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells. J Cell Biol 123: 209–221.
16. ZhengL, ZhangJ, CarthewRW (1995) frizzled regulates mirror-symmetric pattern formation in the Drosophila eye. Development 121: 3045–3055.
17. LawrencePA, CasalJ, StruhlG (2004) Cell interactions and planar polarity in the abdominal epidermis of Drosophila. Development 131: 4651–4664.
18. HoganJ, ValentineM, CoxC, DoyleK, CollierS (2011) Two frizzled planar cell polarity signals in the Drosophila wing are differentially organized by the Fat/Dachsous pathway. PLoS Genet 7: e1001305.
19. ValentineM, CollierS (2011) Planar cell polarity and tissue design: Shaping the Drosophila wing membrane. Fly (Austin) 5: 316–321.
20. StruttH, SearleE, Thomas-MacArthurV, BrookfieldR, StruttD (2013) A Cul-3-BTB ubiquitination pathway regulates junctional levels and asymmetry of core planar polarity proteins. Development 140: 1693–1702.
21. RabutG, PeterM (2008) Function and regulation of protein neddylation. ‘Protein modifications: beyond the usual suspects’ review series. EMBO Rep 9: 969–976.
22. FeiguinF, HannusM, MlodzikM, EatonS (2001) The ankyrin-repeat protein Diego mediates Frizzled-dependent planar polarisation. Dev Cell 1: 93–101.
23. BastockR, StruttH, StruttD (2003) Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development 130: 3007–3014.
24. NarimatsuM, BoseR, PyeM, ZhangL, MillerB, et al. (2009) Regulation of planar cell polarity by Smurf ubiquitin ligases. Cell 137: 295–307.
25. ZhangFL, CaseyPJ (1996) Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 65: 241–269.
26. HancockJF, CadwalladerK, PatersonH, MarshallCJ (1991) A CAAX or a CAAL motif and a second signal are sufficient for plasma membrane targeting of ras proteins. EMBO J 10: 4033–4039.
27. HancockJF, PatersonH, MarshallCJ (1990) A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane. Cell 63: 133–139.
28. LinYY, GubbD (2009) Molecular dissection of Drosophila Prickle isoforms distinguishes their essential and overlapping roles in planar cell polarity. Dev Biol 325: 386–399.
29. VeemanMT, SlusarskiDC, KaykasA, Hallagan LouieS, MoonRT, et al. (2003) Zebrafish Prickle, a modulator of noncanonical Wnt/Fz signalling, regulates gastrulation movements. Curr Biol 13: 680–685.
30. TaoH, InoueK, KiyonariH, BassukAG, AxelrodJD, et al. (2012) Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis. Dev Biol 364: 138–148.
31. BordierC (1981) Phase separation of integral membrane proteins in Triton X-114 solution. J Biol Chem 256: 1604–1607.
32. StruttD, StruttH (2007) Differential activities of the core planar polarity proteins during Drosophila wing patterning. Dev Biol 302: 181–194.
33. KholodenkoBN, HoekJB, WesterhoffHV (2000) Why cytoplasmic signalling proteins should be recruited to cell membranes. Trends Cell Biol 10: 173–178.
34. StruttD, JohnsonR, CooperK, BrayS (2002) Asymmetric localisation of Frizzled and the determination of Notch-dependent cell fate in the Drosophila eye. Curr Biol 12: 813–824.
35. DasG, Reynolds-KenneallyJ, MlodzikM (2002) The atypical cadherin Flamingo links Frizzled and Notch signaling in planar polarity establishment in the Drosophila eye. Dev Cell 2: 655–666.
36. CooperMY, BraySJ (1999) Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye. Nature 397: 526–530.
37. FantoM, MlodzikM (1999) Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye. Nature 397: 523–526.
38. TomlinsonA, StruhlG (1999) Decoding vectorial information from a gradient: sequential rôles of the receptors Frizzled and Notch in establishing planar polarity in the Drosophila eye. Development 126: 5725–5738.
39. StruttH, StruttD (2008) Differential stability of Flamingo protein complexes underlies the establishment of planar polarity. Curr Biol 18: 1555–1564.
40. BishopSA, KleinT, Martinez-AriasA, CousoJP (1999) Composite signalling from Serrate and Delta establishes leg segments in Drosophila through Notch. Development 126: 2993–3003.
41. CapillaA, JohnsonR, DanielsM, BenaventeM, BraySJ, et al. (2012) Planar cell polarity controls directional Notch signaling in the Drosophila leg. Development 139: 2584–2593.
42. TomlinsonA, ReadyDF (1987) Neuronal differentiation in the Drosophila ommatidium. Dev Biol 120: 366–376.
43. StruttDI (2001) Asymmetric localisation of Frizzled and the establishment of cell polarity in the Drosophila wing. Mol Cell 7: 367–375.
44. UsuiT, ShimaY, ShimadaY, HiranoS, BurgessRW, et al. (1999) Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 98: 585–595.
45. WarringtonSJ, StruttH, StruttD (2013) The Frizzled-dependent planar polarity pathway locally promotes E-cadherin turnover via recruitment of RhoGEF2. Development 140: 1045–1054.
46. OdaH, UemuraT, HaradaY, IwaiY, TakeichiM (1994) A Drosophila homolog of cadherin associated with Armadillo and essential for embryonic cell-cell adhesion. Dev Biol 165: 716–726.
47. BastockR, StruttD (2007) The planar polarity pathway promotes coordinated cell migration during Drosophila oogenesis. Development 134: 3055–3064.
48. SantosAC, LehmannR (2004) Isoprenoids control germ cell migration downstream of HMGCoA reductase. Dev Cell 6: 283–293.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2013 Číslo 7
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- The Cohesion Protein SOLO Associates with SMC1 and Is Required for Synapsis, Recombination, Homolog Bias and Cohesion and Pairing of Centromeres in Drosophila Meiosis
- Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry
- Independent Evolution of Transcriptional Inactivation on Sex Chromosomes in Birds and Mammals
- SLC26A4 Targeted to the Endolymphatic Sac Rescues Hearing and Balance in Mutant Mice