Mitogen-Activated Protein Kinase (MAPK) Pathway Regulates Branching by Remodeling Epithelial Cell Adhesion

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Development of the ureter and collecting ducts of the kidney requires extensive growth and branching of an epithelial tube, the ureteric bud. While many genes that control this process are known, the intracellular signaling pathways that underlie renal morphogenesis remain poorly understood. The cellular changes that contribute to ureteric bud morphogenesis, such as adhesion and movements, are guided by intracellular signaling triggered by stimuli at the cell surface. Mitogen-activated protein kinase (MAPK) pathway is known to regulate proliferation in general, but its precise functions during different cell cycle phases are debatable. Moreover, the role of MAPK activity in control of cell adhesion has been demonstrated in cultured cells, but such regulation in vivo remains to be elucidated. Here, we examine the importance of the MAPK activity in ureteric bud branching, and find that simultaneous lack of Mek1 and Mek2 genes allows elongation of the bud but specifically arrests new branch formation. We show that lack of MAPK activity leads to changes in focal adhesion molecules and E-cadherin mediated cell adhesion and delay in cell cycle progression. Our findings may help to understand the origins of certain congenital malformations in humans.

Vyšlo v časopise: Mitogen-Activated Protein Kinase (MAPK) Pathway Regulates Branching by Remodeling Epithelial Cell Adhesion. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004193
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004193

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Zdroje

1. Saxen L (1987) Organogenesis of the Kidney. Cambridge: Cambridge University Press.

2. CostantiniF, KopanR (2010) Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell 18 : 698–712.

3. CostantiniF (2012) Genetic controls and cellular behaviors in branching morphogenesis of the renal collecting system. Wiley Interdiscip Rev Dev Biol 1 : 693–713.

4. SchuchardtA, D'AgatiV, Larsson-BlombergL, CostantiniF, PachnisV (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367 : 380–383.

5. SainioK, SuvantoP, DaviesJ, WartiovaaraJ, WartiovaaraK, et al. (1997) Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium. Development 124 : 4077–4087.

6. ZhaoH, KeggH, GradyS, TruongHT, RobinsonML, et al. (2004) Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Dev Biol 276 : 403–415.

7. MichosO, CebrianC, HyinkD, GrieshammerU, WilliamsL, et al. (2010) Kidney development in the absence of Gdnf and Spry1 requires Fgf10. PLoS Genet 6: e1000809.

8. SongR, El-DahrSS, YosypivIV (2011) Receptor tyrosine kinases in kidney development. J Signal Transduct 2011 : 869281.

9. TangMJ, CaiY, TsaiSJ, WangYK, DresslerGR (2002) Ureteric bud outgrowth in response to RET activation is mediated by phosphatidylinositol 3-kinase. Dev Biol 243 : 128–136.

10. FisherCE, MichaelL, BarnettMW, DaviesJA (2001) Erk MAP kinase regulates branching morphogenesis in the developing mouse kidney. Development 128 : 4329–4338.

11. WatanabeT, CostantiniF (2004) Real-time analysis of ureteric bud branching morphogenesis in vitro. Dev Biol 271 : 98–108.

12. WilleckeR, HeubergerJ, GrossmannK, MichosO, Schmidt-OttK, et al. (2011) The tyrosine phosphatase Shp2 acts downstream of GDNF/Ret in branching morphogenesis of the developing mouse kidney. Dev Biol 360 : 310–317.

13. KimD, DresslerGR (2007) PTEN modulates GDNF/RET mediated chemotaxis and branching morphogenesis in the developing kidney. Dev Biol 307 : 290–299.

14. JainS, EncinasM, JohnsonEMJr, MilbrandtJ (2006) Critical and distinct roles for key RET tyrosine docking sites in renal development. Genes Dev 20 : 321–333.

15. HoshiM, BatourinaE, MendelsohnC, JainS (2012) Novel mechanisms of early upper and lower urinary tract patterning regulated by RetY1015 docking tyrosine in mice. Development 139 : 2405–2415.

16. de GraaffE, SrinivasS, KilkennyC, D'AgatiV, MankooBS, et al. (2001) Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis. Genes Dev 15 : 2433–2444.

17. WongA, BogniS, KotkaP, de GraaffE, D'AgatiV, et al. (2005) Phosphotyrosine 1062 is critical for the in vivo activity of the Ret9 receptor tyrosine kinase isoform. Mol Cell Biol 25 : 9661–9673.

18. MichaelL, DaviesJA (2004) Pattern and regulation of cell proliferation during murine ureteric bud development. J Anat 204 : 241–255.

19. PackardA, GeorgasK, MichosO, RiccioP, CebrianC, et al. (2013) Luminal Mitosis Drives Epithelial Cell Dispersal within the Branching Ureteric Bud. Dev Cell 27 : 319–330.

20. ChiX, MichosO, ShakyaR, RiccioP, EnomotoH, et al. (2009) Ret-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis. Dev Cell 17 : 199–209.

21. KuureS, CebrianC, MachingoQ, LuBC, ChiX, et al. (2010) Actin depolymerizing factors cofilin1 and destrin are required for ureteric bud branching morphogenesis. PLoS Genet 6: e1001176.

22. RoskoskiRJr (2012) MEK1/2 dual-specificity protein kinases: structure and regulation. Biochem Biophys Res Commun 417 : 5–10.

23. RoskoskiRJr (2012) ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res 66 : 105–143.

24. IshibeS, JolyD, ZhuX, CantleyLG (2003) Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Mol Cell 12 : 1275–1285.

25. IshibeS, JolyD, LiuZX, CantleyLG (2004) Paxillin serves as an ERK-regulated scaffold for coordinating FAK and Rac activation in epithelial morphogenesis. Mol Cell 16 : 257–267.

26. PengX, NelsonES, MaiersJL, DeMaliKA (2011) New insights into vinculin function and regulation. Int Rev Cell Mol Biol 287 : 191–231.

27. DubrovskyiO, TianX, PoroykoV, YakubovB, BirukovaAA, et al. (2012) Identification of paxillin domains interacting with beta-catenin. FEBS Lett 586 : 2294–2299.

28. le DucQ, ShiQ, BlonkI, SonnenbergA, WangN, et al. (2010) Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J Cell Biol 189 : 1107–1115.

29. PengX, CuffLE, LawtonCD, DeMaliKA (2010) Vinculin regulates cell-surface E-cadherin expression by binding to beta-catenin. J Cell Sci 123 : 567–577.

30. BissonauthV, RoyS, GravelM, GuillemetteS, CharronJ (2006) Requirement for Map2k1 (Mek1) in extra-embryonic ectoderm during placentogenesis. Development 133 : 3429–3440.

31. BelangerLF, RoyS, TremblayM, BrottB, SteffAM, et al. (2003) Mek2 is dispensable for mouse growth and development. Mol Cell Biol 23 : 4778–4787.

32. SchollFA, DumesicPA, BarraganDI, HaradaK, BissonauthV, et al. (2007) Mek1/2 MAPK kinases are essential for Mammalian development, homeostasis, and Raf-induced hyperplasia. Dev Cell 12 : 615–629.

33. LuBC, CebrianC, ChiX, KuureS, KuoR, et al. (2009) Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nat Genet 41 : 1295–1302.

34. OlaR, JakobsonM, KvistJ, PeralaN, KuureS, et al. (2011) The GDNF Target Vsnl1 Marks the Ureteric Tip. J Am Soc Nephrol 22 : 274–284.

35. CabritaMA, ChristoforiG (2008) Sprouty proteins, masterminds of receptor tyrosine kinase signaling. Angiogenesis 11 : 53–62.

36. ChambardJC, LeflochR, PouyssegurJ, LenormandP (2007) ERK implication in cell cycle regulation. Biochim Biophys Acta 1773 : 1299–1310.

37. ShinoharaM, MikhailovAV, Aguirre-GhisoJA, RiederCL (2006) Extracellular signal-regulated kinase 1/2 activity is not required in mammalian cells during late G2 for timely entry into or exit from mitosis. Mol Biol Cell 17 : 5227–5240.

38. GuadagnoTM, FerrellJEJr (1998) Requirement for MAPK activation for normal mitotic progression in Xenopus egg extracts. Science 282 : 1312–1315.

39. HorneMM, GuadagnoTM (2003) A requirement for MAP kinase in the assembly and maintenance of the mitotic spindle. J Cell Biol 161 : 1021–1028.

40. LavoieJN, L'AllemainG, BrunetA, MullerR, PouyssegurJ (1996) Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. J Biol Chem 271 : 20608–20616.

41. WeberJD, RabenDM, PhillipsPJ, BaldassareJJ (1997) Sustained activation of extracellular-signal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G1 phase. Biochem J 326 (Pt 1): 61–68.

42. BaraschJ, PresslerL, ConnorJ, MalikA (1996) A ureteric bud cell line induces nephrogenesis in two steps by two distinct signals. Am J Physiol 271: F50–F61.

43. KuureS (2012) Analysis of migration in primary ureteric bud epithelial cells. Methods Mol Biol 886 : 147–155.

44. CaveyM, RauziM, LennePF, LecuitT (2008) A two-tiered mechanism for stabilization and immobilization of E-cadherin. Nature 453 : 751–756.

45. ParedesJ, FigueiredoJ, AlbergariaA, OliveiraP, CarvalhoJ, et al. (2012) Epithelial E -⁠ and P-cadherins: role and clinical significance in cancer. Biochim Biophys Acta 1826 : 297–311.

46. KeilR, SchulzJ, HatzfeldM (2013) p0071/PKP4, a multifunctional protein coordinating cell adhesion with cytoskeletal organization. Biol Chem 394 : 1005–1017.

47. LiJ, AnanthapanyasutW, YuAS (2011) Claudins in renal physiology and disease. Pediatr Nephrol 26 : 2133–2142.

48. NadeauV, GuillemetteS, BelangerLF, JacobO, RoyS, et al. (2009) Map2k1 and Map2k2 genes contribute to the normal development of syncytiotrophoblasts during placentation. Development 136 : 1363–1374.

49. LeflochR, PouyssegurJ, LenormandP (2008) Single and combined silencing of ERK1 and ERK2 reveals their positive contribution to growth signaling depending on their expression levels. Mol Cell Biol 28 : 511–527.

50. CostantiniF (2010) GDNF/Ret signaling and renal branching morphogenesis: From mesenchymal signals to epithelial cell behaviors. Organogenesis 6 : 252–262.

51. LewellisSW, KnautH (2012) Attractive guidance: how the chemokine SDF1/CXCL12 guides different cells to different locations. Semin Cell Dev Biol 23 : 333–340.

52. MelocheS, PouyssegurJ (2007) The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1 -⁠ to S-phase transition. Oncogene 26 : 3227–3239.

53. de BecoS, AmblardF, CoscoyS (2012) New insights into the regulation of E-cadherin distribution by endocytosis. Int Rev Cell Mol Biol 295 : 63–108.

54. FujitaY, KrauseG, ScheffnerM, ZechnerD, LeddyHE, et al. (2002) Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat Cell Biol 4 : 222–231.

55. QuadriSK (2012) Cross talk between focal adhesion kinase and cadherins: role in regulating endothelial barrier function. Microvasc Res 83 : 3–11.

56. SerrelsA, CanelM, BruntonVG, FrameMC (2011) Src/FAK-mediated regulation of E-cadherin as a mechanism for controlling collective cell movement: insights from in vivo imaging. Cell Adh Migr 5 : 360–365.

57. ThomasWA, BoscherC, ChuYS, CuvelierD, Martinez-RicoC, et al. (2013) alpha-Catenin and vinculin cooperate to promote high E-cadherin-based adhesion strength. J Biol Chem 288 : 4957–4969.

58. KuureS, SainioK, VuolteenahoR, IlvesM, WartiovaaraK, et al. (2005) Crosstalk between Jagged1 and GDNF/Ret/GFRalpha1 signalling regulates ureteric budding and branching. Mech Dev 122 : 765–780.

59. Wilkinson DG (1992) Whole mount in situ hybridization of vertebrate embryos. In: Wilkinson DG, editor. In situ hybridization: a practical approach. Oxford: IRL Press. pp. 75–83.

60. Runeberg-RoosP, VirtanenH, SaarmaM (2007) RET(MEN 2B) is active in the endoplasmic reticulum before reaching the cell surface. Oncogene 26 : 7909–7915.