Proper Actin Ring Formation and Septum Constriction Requires Coordinated Regulation of SIN and MOR Pathways through the Germinal Centre Kinase MST-1

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Cytokinesis is a fundamental cellular process essential for cell proliferation of uni- and multicellular organisms. The molecular pathways that regulate cytokinesis are highly complex and involve a large number of components that form elaborate interactive networks. The fungal septation initiation network (SIN) functions as tripartite kinase cascade that connects cell cycle progression with the control of cell division. Mis-regulation of the homologous Hippo pathway in animals results in excessive proliferation and formation of tumors, underscoring the conservation and importance of these kinase networks. A second morphogenesis (MOR) pathway involves homologous components and is controlling cell polarity in fungi and higher eukaryotes. Here we show that the promiscuous functioning Ste20-related kinase MST-1 has a dual role in regulating SIN and MOR network function. Moreover, SIN and MOR coordination through MST-1 can be achieved in an enzyme-independent manner through hetero-dimerization of germinal centre kinases, providing an additional level for activity regulation of signaling networks that is not dependent on phosphate transfer. Given the functional conservation of NDR kinase signaling modules and their regulation, our work may define general mechanisms by which NDR kinase pathway are coordinated in fungi and higher eukaryotes.

Vyšlo v časopise: Proper Actin Ring Formation and Septum Constriction Requires Coordinated Regulation of SIN and MOR Pathways through the Germinal Centre Kinase MST-1. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004306
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004306

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Zdroje

1. ParkHO, BiE (2007) Central roles of small GTPases in the development of cell polarity in yeast and beyond. Microbiol Mol Biol Rev 71: 48–96.

2. PollardTD, WuJQ (2010) Understanding cytokinesis: lessons from fission yeast. Nat Rev Mol Cell Biol 11: 149–155.

3. BarrFA, GrunebergU (2007) Cytokinesis: placing and making the final cut. Cell 131: 847–860.

4. HergovichA, StegertMR, SchmitzD, HemmingsBA (2006) NDR kinases regulate essential cell processes from yeast to humans. Nat Rev Mol Cell Biol 7: 253–264.

5. MaerzS, SeilerS (2010) Tales of RAM and MOR: NDR kinase signaling in fungal morphogenesis. Curr Opin Microbiol 13: 663–671.

6. HergovichA (2012) Mammalian Hippo signalling: a kinase network regulated by protein-protein interactions. Biochem Soc Trans 40: 124–128.

7. HergovichA, HemmingsBA (2012) Hippo signalling in the G2/M cell cycle phase: lessons learned from the yeast MEN and SIN pathways. Semin Cell Dev Biol 23: 794–802.

8. KrappA, SimanisV (2008) An overview of the fission yeast septation initiation network (SIN). Biochem Soc Trans 36: 411–415.

9. CliffordDM, ChenCT, RobertsRH, FeoktistovaA, WolfeBA, et al. (2008) The role of Cdc14 phosphatases in the control of cell division. Biochem Soc Trans 36: 436–438.

10. MeitingerF, PalaniS, PereiraG (2012) The power of MEN in cytokinesis. Cell Cycle 11: 219–228.

11. WeissEL (2012) Mitotic exit and separation of mother and daughter cells. Genetics 192: 1165–1202.

12. SchneperL, KraussA, MiyamotoR, FangS, BroachJR (2004) The Ras/protein kinase A pathway acts in parallel with the Mob2/Cbk1 pathway to effect cell cycle progression and proper bud site selection. Eukaryot Cell 3: 108–120.

13. DasM, WileyDJ, MedinaS, VincentHA, LarreaM, et al. (2007) Regulation of cell diameter, For3p localization, and cell symmetry by fission yeast Rho-GAP Rga4p. Mol Biol Cell 18: 2090–2101.

14. VogtN, SeilerS (2008) The RHO1-specific GTPase-activating protein LRG1 regulates polar tip growth in parallel to Ndr kinase signaling in Neurospora. Mol Biol Cell 19: 4554–4569.

15. DasM, WileyDJ, ChenX, ShahK, VerdeF (2009) The conserved NDR kinase Orb6 controls polarized cell growth by spatial regulation of the small GTPase Cdc42. Curr Biol 19: 1314–1319.

16. BidlingmaierS, WeissEL, SeidelC, DrubinDG, SnyderM (2001) The Cbk1p pathway is important for polarized cell growth and cell separation in Saccharomyces cerevisiae. Mol Cell Biol 21: 2449–2462.

17. MazankaE, AlexanderJ, YehBJ, CharoenpongP, LoweryDM, et al. (2008) The NDR/LATS family kinase Cbk1 directly controls transcriptional asymmetry. PLoS Biol 6: e203.

18. Gutierrez-EscribanoP, ZeidlerU, SuarezMB, Bachellier-BassiS, Clemente-BlancoA, et al. (2012) The NDR/LATS kinase Cbk1 controls the activity of the transcriptional regulator Bcr1 during biofilm formation in Candida albicans. PLoS Pathog 8: e1002683.

19. RayS, KumeK, GuptaS, GeW, BalasubramanianM, et al. (2010) The mitosis-to-interphase transition is coordinated by cross talk between the SIN and MOR pathways in Schizosaccharomyces pombe. J Cell Biol 190: 793–805.

20. GuptaS, McCollumD (2011) Crosstalk between NDR kinase pathways coordinates cell cycle dependent actin rearrangements. Cell Div 6: 19.

21. GuptaS, Mana-CapelliS, McLeanJR, ChenCT, RayS, et al. (2013) Identification of SIN pathway targets reveals mechanisms of crosstalk between NDR kinase pathways. Curr Biol 23: 333–338.

22. LeonhardK, NurseP (2005) Ste20/GCK kinase Nak1/Orb3 polarizes the actin cytoskeleton in fission yeast during the cell cycle. J Cell Sci 118: 1033–1044.

23. KanaiM, KumeK, MiyaharaK, SakaiK, NakamuraK, et al. (2005) Fission yeast MO25 protein is localized at SPB and septum and is essential for cell morphogenesis. EMBO J 24: 3012–3025.

24. CornilsH, KohlerRS, HergovichA, HemmingsBA (2011) Human NDR kinases control G(1)/S cell cycle transition by directly regulating p21 stability. Mol Cell Biol 31: 1382–1395.

25. VisserS, YangX (2010) LATS tumor suppressor: a new governor of cellular homeostasis. Cell Cycle 9: 3892–3903.

26. HergovichA, CornilsH, HemmingsBA (2008) Mammalian NDR protein kinases: from regulation to a role in centrosome duplication. Biochim Biophys Acta 1784: 3–15.

27. HarrisSD (2001) Septum formation in Aspergillus nidulans. Curr Opin Microbiol 4: 736–739.

28. SeilerS, Justa-SchuchD (2010) Conserved components, but distinct mechanisms for the placement and assembly of the cell division machinery in unicellular and filamentous ascomycetes. Mol Microbiol 78: 1058–1076.

29. RiquelmeM, YardenO, Bartnicki-GarciaS, BowmanB, Castro-LongoriaE, et al. (2011) Architecture and development of the Neurospora crassa hypha - a model cell for polarized growth. Fungal Biol 115: 446–474.

30. WolkowTD, HarrisSD, HamerJE (1996) Cytokinesis in Aspergillus nidulans is controlled by cell size, nuclear positioning and mitosis. J Cell Sci 109 (Pt 8) 2179–2188.

31. MinkePF, LeeIH, PlamannM (1999) Microscopic analysis of Neurospora ropy mutants defective in nuclear distribution. Fungal Genet Biol 28: 55–67.

32. KimJM, ZengCJ, NayakT, ShaoR, HuangAC, et al. (2009) Timely septation requires SNAD-dependent spindle pole body localization of the septation initiation network components in the filamentous fungus Aspergillus nidulans. Mol Biol Cell 20: 2874–2884.

33. RasmussenCG, GlassNL (2005) A Rho-type GTPase, rho-4, is required for septation in Neurospora crassa. Eukaryot Cell 4: 1913–1925.

34. SiH, Justa-SchuchD, SeilerS, HarrisSD (2010) Regulation of septum formation by the Bud3-Rho4 GTPase module in Aspergillus nidulans. Genetics 185: 165–176.

35. Justa-SchuchD, HeiligY, RichthammerC, SeilerS (2010) Septum formation is regulated by the RHO4-specific exchange factors BUD3 and RGF3 and by the landmark protein BUD4 in Neurospora crassa. Mol Microbiol 76: 220–235.

36. SeilerS, PlamannM (2003) The genetic basis of cellular morphogenesis in the filamentous fungus Neurospora crassa. Mol Biol Cell 14: 4352–4364.

37. YardenO, PlamannM, EbboleDJ, YanofskyC (1992) cot-1, a gene required for hyphal elongation in Neurospora crassa, encodes a protein kinase. EMBO J 11: 2159–2166.

38. SeilerS, VogtN, ZivC, GorovitsR, YardenO (2006) The STE20/germinal center kinase POD6 interacts with the NDR kinase COT1 and is involved in polar tip extension in Neurospora crassa. Mol Biol Cell 17: 4080–4092.

39. MaerzS, DettmannA, ZivC, LiuY, ValeriusO, et al. (2009) Two NDR kinase-MOB complexes function as distinct modules during septum formation and tip extension in Neurospora crassa. Mol Microbiol 74: 707–723.

40. RichthammerC, EnseleitM, Sanchez-LeonE, MarzS, HeiligY, et al. (2012) RHO1 and RHO2 share partially overlapping functions in the regulation of cell wall integrity and hyphal polarity in Neurospora crassa. Mol Microbiol 85: 716–733.

41. MaerzS, DettmannA, SeilerS (2012) Hydrophobic motif phosphorylation coordinates activity and polar localization of the Neurospora crassa nuclear Dbf2-related kinase COT1. Mol Cell Biol 32: 2083–2098.

42. DettmannA, IllgenJ, MarzS, SchurgT, FleissnerA, et al. (2012) The NDR kinase scaffold HYM1/MO25 is essential for MAK2 map kinase signaling in Neurospora crassa. PLoS Genet 8: e1002950.

43. HeiligY, SchmittK, SeilerS (2013) Phospho-Regulation of the Neurospora crassa Septation Initiation Network. PLoS One 8: e79464.

44. DanI, WatanabeNM, KusumiA (2001) The Ste20 group kinases as regulators of MAP kinase cascades. Trends Cell Biol 11: 220–230.

45. HuangTY, MarkleyNA, YoungD (2003) Nak1, an essential germinal center (GC) kinase regulates cell morphology and growth in Schizosaccharomyces pombe. J Biol Chem 278: 991–997.

46. NelsonB, KurischkoC, HoreckaJ, ModyM, NairP, et al. (2003) RAM: a conserved signaling network that regulates Ace2p transcriptional activity and polarized morphogenesis. Mol Biol Cell 14: 3782–3803.

47. GuertinDA, ChangL, IrshadF, GouldKL, McCollumD (2000) The role of the sid1p kinase and cdc14p in regulating the onset of cytokinesis in fission yeast. EMBO J 19: 1803–1815.

48. GoshimaT, KumeK, KoyanoT, OhyaY, TodaT, et al. (2010) Fission yeast germinal center (GC) kinase Ppk11 interacts with Pmo25 and plays an auxiliary role in concert with the morphogenesis Orb6 network (MOR) in cell morphogenesis. J Biol Chem 285: 35196–35205.

49. DvashE, Kra-OzG, ZivC, CarmeliS, YardenO (2010) The NDR kinase DBF-2 is involved in regulation of mitosis, conidial development, and glycogen metabolism in Neurospora crassa. Eukaryot Cell 9: 502–513.

50. BerepikiA, LichiusA, ReadND (2011) Actin organization and dynamics in filamentous fungi. Nat Rev Microbiol 9: 876–887.

51. BalasubramanianMK, SrinivasanR, HuangY, NgKH (2012) Comparing contractile apparatus-driven cytokinesis mechanisms across kingdoms. Cytoskeleton (Hoboken) 69: 942–956.

52. Delgado-AlvarezDL, Callejas-NegreteOA, GomezN, FreitagM, RobersonRW, et al. (2010) Visualization of F-actin localization and dynamics with live cell markers in Neurospora crassa. Fungal Genet Biol 47: 573–586.

53. Mourino-PérezR (2013) Septum development in filamentous ascomycetes. Fungal Biology Reviews 27: 1–9.

54. RodrigoG, ElenaSF (2011) Structural discrimination of robustness in transcriptional feedforward loops for pattern formation. PLoS One 6: e16904.

55. JohnsonAE, McCollumD, GouldKL (2012) Polar opposites: Fine-tuning cytokinesis through SIN asymmetry. Cytoskeleton (Hoboken) 69: 686–699.

56. StegertMR, HergovichA, TamaskovicR, BichselSJ, HemmingsBA (2005) Regulation of NDR protein kinase by hydrophobic motif phosphorylation mediated by the mammalian Ste20-like kinase MST3. Mol Cell Biol 25: 11019–11029.

57. JansenJM, BarryMF, YooCK, WeissEL (2006) Phosphoregulation of Cbk1 is critical for RAM network control of transcription and morphogenesis. J Cell Biol 175: 755–766.

58. ZivC, Kra-OzG, GorovitsR, MarzS, SeilerS, et al. (2009) Cell elongation and branching are regulated by differential phosphorylation states of the nuclear Dbf2-related kinase COT1 in Neurospora crassa. Mol Microbiol 74: 974–989.

59. EmotoK, ParrishJZ, JanLY, JanYN (2006) The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance. Nature 443: 210–213.

60. HergovichA, HemmingsBA (2009) Mammalian NDR/LATS protein kinases in hippo tumor suppressor signaling. Biofactors 35: 338–345.

61. VichalkovskiA, GreskoE, CornilsH, HergovichA, SchmitzD, et al. (2008) NDR kinase is activated by RASSF1A/MST1 in response to Fas receptor stimulation and promotes apoptosis. Curr Biol 18: 1889–1895.

62. McCluskeyK (2003) The Fungal Genetics Stock Center: from molds to molecules. Adv Appl Microbiol 52: 245–262.

63. FreitagM, HickeyPC, RajuNB, SelkerEU, ReadND (2004) GFP as a tool to analyze the organization, dynamics and function of nuclei and microtubules in Neurospora crassa. Fungal Genet Biol 41: 897–910.

64. KawabataT, KatoA, SuzukiK, InoueH (2007) Neurosprora crassa RAD5 homologue, mus-41, inactivation results in higher sensitivity to mutagens but has little effect on PCNA-ubiquitylation in response to UV-irradiation. Curr Genet 52: 125–135.

65. KawabataT, InoueH (2007) Detection of physical interactions by immunoprecipitation of FLAG- and HA-tagged proteins expressed at the his-3 locus in Neurospora crassa. Fungal Genetics Newsletter 54: 5–8.

66. MaddiA, DettmanA, FuC, SeilerS, FreeSJ (2012) WSC-1 and HAM-7 are MAK-1 MAP kinase pathway sensors required for cell wall integrity and hyphal fusion in Neurospora crassa. PLoS One 7: e42374.

67. MaerzS, FunakoshiY, NegishiY, SuzukiT, SeilerS (2010) The Neurospora peptide:N-glycanase ortholog PNG1 is essential for cell polarity despite its lack of enzymatic activity. J Biol Chem 285: 2326–2332.

68. DettmannA, HeiligY, LudwigS, SchmittK, IllgenJ, et al. (2013) HAM-2 and HAM-3 are central for the assembly of the Neurospora STRIPAK complex at the nuclear envelope and regulate nuclear accumulation of the MAP kinase MAK-1 in a MAK-2-dependent manner. Mol Microbiol 90: 796–812.

69. Araujo-PalomaresCL, RichthammerC, SeilerS, Castro-LongoriaE (2011) Functional characterization and cellular dynamics of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. PLoS One 6: e27148.

70. RiquelmeM, BredewegEL, Callejas-NegreteO, RobersonRW, LudwigS, et al. (2014) The Neurospora crassa exocyst complex tethers Spitzenkorper vesicles to the apical plasma membrane during polarized growth. Mol Biol Cell In press: doi:10.1091/mbc.E13-06-0299

71. MillwardTA, HeizmannCW, SchaferBW, HemmingsBA (1998) Calcium regulation of Ndr protein kinase mediated by S100 calcium-binding proteins. EMBO J 17: 5913–5922.