#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The NDR Kinase Scaffold HYM1/MO25 Is Essential for MAK2 MAP Kinase Signaling in


Cell communication is essential for eukaryotic development, but our knowledge of molecules and mechanisms required for intercellular communication is fragmentary. In particular, the connection between signal sensing and regulation of cell polarity is poorly understood. In the filamentous ascomycete Neurospora crassa, germinating spores mutually attract each other and subsequently fuse. During these tropic interactions, the two communicating cells rapidly alternate between two different physiological states, probably associated with signal delivery and response. The MAK2 MAP kinase cascade mediates cell–cell signaling. Here, we show that the conserved scaffolding protein HYM1/MO25 controls the cell shape-regulating NDR kinase module as well as the signal-receiving MAP kinase cascade. HYM1 functions as an integral part of the COT1 NDR kinase complex to regulate the interaction with its upstream kinase POD6 and thereby COT1 activity. In addition, HYM1 interacts with NRC1, MEK2, and MAK2, the three kinases of the MAK2 MAP kinase cascade, and co-localizes with MAK2 at the apex of growing cells. During cell fusion, the three kinases of the MAP kinase module as well as HYM1 are recruited to the point of cell–cell contact. hym-1 mutants phenocopy all defects observed for MAK2 pathway mutants by abolishing MAK2 activity. An NRC1-MEK2 fusion protein reconstitutes MAK2 signaling in hym-1, while constitutive activation of NRC1 and MEK2 does not. These data identify HYM1 as a novel regulator of the NRC1-MEK2-MAK2 pathway, which may coordinate NDR and MAP kinase signaling during cell polarity and intercellular communication.


Vyšlo v časopise: The NDR Kinase Scaffold HYM1/MO25 Is Essential for MAK2 MAP Kinase Signaling in. PLoS Genet 8(9): e32767. doi:10.1371/journal.pgen.1002950
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002950

Souhrn

Cell communication is essential for eukaryotic development, but our knowledge of molecules and mechanisms required for intercellular communication is fragmentary. In particular, the connection between signal sensing and regulation of cell polarity is poorly understood. In the filamentous ascomycete Neurospora crassa, germinating spores mutually attract each other and subsequently fuse. During these tropic interactions, the two communicating cells rapidly alternate between two different physiological states, probably associated with signal delivery and response. The MAK2 MAP kinase cascade mediates cell–cell signaling. Here, we show that the conserved scaffolding protein HYM1/MO25 controls the cell shape-regulating NDR kinase module as well as the signal-receiving MAP kinase cascade. HYM1 functions as an integral part of the COT1 NDR kinase complex to regulate the interaction with its upstream kinase POD6 and thereby COT1 activity. In addition, HYM1 interacts with NRC1, MEK2, and MAK2, the three kinases of the MAK2 MAP kinase cascade, and co-localizes with MAK2 at the apex of growing cells. During cell fusion, the three kinases of the MAP kinase module as well as HYM1 are recruited to the point of cell–cell contact. hym-1 mutants phenocopy all defects observed for MAK2 pathway mutants by abolishing MAK2 activity. An NRC1-MEK2 fusion protein reconstitutes MAK2 signaling in hym-1, while constitutive activation of NRC1 and MEK2 does not. These data identify HYM1 as a novel regulator of the NRC1-MEK2-MAK2 pathway, which may coordinate NDR and MAP kinase signaling during cell polarity and intercellular communication.


Zdroje

1. DardN, PeterM (2006) Scaffold proteins in MAP kinase signaling: more than simple passive activating platforms. Bioessays 28: 146–156.

2. SaitoH (2010) Regulation of cross-talk in yeast MAPK signaling pathways. Curr Opin Microbiol 13: 677–683.

3. MartinH, FlandezM, NombelaC, MolinaM (2005) Protein phosphatases in MAPK signalling: we keep learning from yeast. Mol Microbiol 58: 6–16.

4. KolchW (2005) Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat Rev Mol Cell Biol 6: 827–837.

5. BudayL, TompaP (2010) Functional classification of scaffold proteins and related molecules. FEBS J 277: 4348–4355.

6. GoudreaultM, D'AmbrosioLM, KeanMJ, MullinMJ, LarsenBG, et al. (2009) A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein. Mol Cell Proteomics 8: 157–171.

7. BloemendalS, BernhardsY, BarthoK, DettmannA, VoigtO, et al. (2012) A homologue of the human STRIPAK complex controls sexual development in fungi. Mol Microbiol 84: 310–323.

8. BardwellL (2005) A walk-through of the yeast mating pheromone response pathway. Peptides 26: 339–350.

9. DohlmanHG, SlessarevaJE (2006) Pheromone signaling pathways in yeast. Sci STKE 2006: cm6.

10. PandeyA, RocaMG, ReadND, GlassNL (2004) Role of a mitogen-activated protein kinase pathway during conidial germination and hyphal fusion in Neurospora crassa. Eukaryot Cell 3: 348–358.

11. LiD, BobrowiczP, WilkinsonHH, EbboleDJ (2005) A mitogen-activated protein kinase pathway essential for mating and contributing to vegetative growth in Neurospora crassa. Genetics 170: 1091–1104.

12. MaerzS, ZivC, VogtN, HelmstaedtK, CohenN, et al. (2008) The nuclear Dbf2-related kinase COT1 and the mitogen-activated protein kinases MAK1 and MAK2 genetically interact to regulate filamentous growth, hyphal fusion and sexual development in Neurospora crassa. Genetics 179: 1313–1325.

13. FleissnerA, LeederAC, RocaMG, ReadND, GlassNL (2009) Oscillatory recruitment of signaling proteins to cell tips promotes coordinated behavior during cell fusion. Proc Natl Acad Sci U S A 106: 19387–19392.

14. LiL, WrightSJ, KrystofovaS, ParkG, BorkovichKA (2007) Heterotrimeric G protein signaling in filamentous fungi. Annu Rev Microbiol 61: 423–452.

15. RispailN, SoanesDM, AntC, CzajkowskiR, GrunlerA, et al. (2009) Comparative genomics of MAP kinase and calcium-calcineurin signalling components in plant and human pathogenic fungi. Fungal Genet Biol 46: 287–298.

16. FleissnerA, SimoninAR, GlassNL (2008) Cell fusion in the filamentous fungus, Neurospora crassa. Methods Mol Biol 475: 21–38.

17. ReadND, LichiusA, ShojiJY, GoryachevAB (2009) Self-signalling and self-fusion in filamentous fungi. Curr Opin Microbiol 12: 608–615.

18. GoryachevAB, LichiusA, WrightGD, ReadND (2012) Excitable behavior can explain the “ping-pong” mode of communication between cells using the same chemoattractant. Bioessays 34: 259–266.

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

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

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

22. ChibaS, IkedaM, KatsunumaK, OhashiK, MizunoK (2009) MST2- and Furry-mediated activation of NDR1 kinase is critical for precise alignment of mitotic chromosomes. Curr Biol 19: 675–681.

23. ZallenJA, PeckolEL, TobinDM, BargmannCI (2000) Neuronal cell shape and neurite initiation are regulated by the Ndr kinase SAX-1, a member of the Orb6/COT-1/warts serine/threonine kinase family. Mol Biol Cell 11: 3177–3190.

24. CongJ, GengW, HeB, LiuJ, CharltonJ, et al. (2001) The furry gene of Drosophila is important for maintaining the integrity of cellular extensions during morphogenesis. Development 128: 2793–2802.

25. DuLL, NovickP (2002) Pag1p, a novel protein associated with protein kinase Cbk1p, is required for cell morphogenesis and proliferation in Saccharomyces cerevisiae. Mol Biol Cell 13: 503–514.

26. HirataD, KishimotoN, SudaM, SogabeY, NakagawaS, et al. (2002) Fission yeast Mor2/Cps12, a protein similar to Drosophila Furry, is essential for cell morphogenesis and its mutation induces Wee1-dependent G(2) delay. EMBO J 21: 4863–4874.

27. 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.

28. 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.

29. 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.

30. AlessiDR, SakamotoK, BayascasJR (2006) LKB1-dependent signaling pathways. Annu Rev Biochem 75: 137–163.

31. HeY, EmotoK, FangX, RenN, TianX, et al. (2005) Drosophila Mob family proteins interact with the related tricornered (Trc) and warts (Wts) kinases. Mol Biol Cell 16: 4139–4152.

32. FilippiBM, de los HerosP, MehellouY, NavratilovaI, GourlayR, et al. (2011) MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases. EMBO J 30: 1730–1741.

33. 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.

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

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. HarrisSD, ReadND, RobersonRW, ShawB, SeilerS, et al. (2005) Polarisome meets spitzenkorper: microscopy, genetics, and genomics converge. Eukaryot Cell 4: 225–229.

41. ViragA, HarrisSD (2006) The Spitzenkorper: a molecular perspective. Mycol Res 110: 4–13.

42. 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.

43. SongY, CheonSA, LeeKE, LeeSY, LeeBK, et al. (2008) Role of the RAM network in cell polarity and hyphal morphogenesis in Candida albicans. Mol Biol Cell 19: 5456–5477.

44. SartorelE, and, Perez-MartinJ (2012) The distinct wiring between cell cycle regulation and the widely conserved Morphogenesis-Related (MOR) pathway in the fungus Ustilago maydis determines the morphological outcome. J Cell Sci doi:10.1242/jcs.107862.

45. KotheGO, FreeSJ (1998) The isolation and characterization of nrc-1 and nrc-2, two genes encoding protein kinases that control growth and development in Neurospora crassa. Genetics 149: 117–130.

46. MaddiA, DettmannA, 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 doi:10.1371/journal.pone.0042374.

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

48. StevensonBJ, RhodesN, ErredeB, SpragueGFJr (1992) Constitutive mutants of the protein kinase STE11 activate the yeast pheromone response pathway in the absence of the G protein. Genes Dev 6: 1293–1304.

49. MuellerP, WeinzierlG, BrachmannA, FeldbruggeM, KahmannR (2003) Mating and pathogenic development of the Smut fungus Ustilago maydis are regulated by one mitogen-activated protein kinase cascade. Eukaryot Cell 2: 1187–1199.

50. BerepikiA, LichiusA, ShojiJY, TilsnerJ, ReadND (2010) F-actin dynamics in Neurospora crassa. Eukaryot Cell 9: 547–557.

51. MaederCI, HinkMA, KinkhabwalaA, MayrR, BastiaensPI, et al. (2007) Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling. Nat Cell Biol 9: 1319–1326.

52. 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.

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

54. HondaS, SelkerEU (2009) Tools for fungal proteomics: multifunctional neurospora vectors for gene replacement, protein expression and protein purification. Genetics 182: 11–23.

55. 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.

56. 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.

57. 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.

58. 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 doi: 10.1371/journal.pone.0027148.

59. SchnabelR, HutterH, MoermanD, SchnabelH (1997) Assessing normal embryogenesis in Caenorhabditis elegans using a 4D microscope: variability of development and regional specification. Dev Biol 184: 234–265.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2012 Číslo 9
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#