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Depletion of a Polo-like Kinase in Candida albicans Activates Cyclase-dependent Hyphal-like Growth

Title:

Depletion of a Polo-like Kinase in Candida albicans Activates Cyclase-dependent Hyphal-like Growth

Bachewich, Catherine (2003) Depletion of a Polo-like Kinase in Candida albicans Activates Cyclase-dependent Hyphal-like Growth. Molecular Biology of the Cell, 14 (5). pp. 2163-2180. ISSN 10591524

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Official URL: http://dx.doi.org/10.1091/mbc.02-05-0076

Abstract

Morphogenesis in the fungal pathogen Candida albicans is an important virulence-determining factor, as a dimorphic switch between yeast and hyphal growth forms can increase pathogenesis. We identified CaCDC5, a cell cycle regulatory polo-like kinase (PLK) in C. albicans and demonstrate that shutting off its expression induced cell cycle defects and dramatic changes in morphology. Cells lacking CaCdc5p were blocked early in nuclear division with very short spindles and unseparated chromatin. GFP-tagged CaCdc5p localized to unseparated spindle pole bodies, the spindle, and chromatin, consistent with a role in spindle elongation at an earlier point in the cell cycle than that described for the homologue Cdc5p in yeast. Strikingly, the cell cycle defects were accompanied by the formation of hyphal-like filaments under yeast growth conditions. Filament growth was determinate, as the filaments started to die after 24 h. The filaments resembled serum-induced hyphae with respect to morphology, organization of cytoplasmic microtubules, localization of nuclei, and expression of hyphal-specific components. Filament formation required CaCDC35, but not EFG1 or CPH1. Similar defects in spindle elongation and a corresponding induction of filaments occurred when yeast cells were exposed to hydroxyurea. Because CaCdc5p does not appear to act as a direct repressor of hyphal growth, the data suggest that a target of CaCdc5p function is associated with hyphal-like development. Thus, an internal, cell cycle–related cue can activate hyphal regulatory networks in Candida.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Article
Refereed:Yes
Authors:Bachewich, Catherine
Journal or Publication:Molecular Biology of the Cell
Date:May 2003
ID Code:7583
Deposited By:DANIELLE DENNIE
Deposited On:11 May 2011 17:33
Last Modified:11 May 2011 17:33
References:
Alexandru, G., Uhlmann, F., Mechtler, K., Poupart, M., and Nasmyth, K. (2001). Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast. Cell 105, 459–472

Backen, A.C., Broadbent, I.D., Fetherston, R.W., Rosamond, J.D.C., Schnell, N.F., and Stark, M.J.R. (2000). Evaluation of the CaMAL promotor for regulated expression of genes in Candida albicans. Yeast 16, 1121–1129

Bai, C., Ramanan, N., Wang, Y.M., and Wang, Y. (2002). Spindle assembly checkpoint component CaMad2p is indispensable for Candida albicans survival and virulence in mice. Mol. Microbiol. 45, 31–44

Bartholomew, C.R., Woo, S.H., Chung, Y.S., Jones, C., and Hardy, C. (2001). Cdc5 interacts with the Wee1 kinase in budding yeast. Mol. Cell. Biol. 21, 4949–4959

Barton, R., and Gull. K. (1988). Variation in cytoplasmic microtubule organization and spindle length between two forms of the dimorphic fungus Candida albicans. J. Cell Sci. 91, 211–220

Bensen, E.S., Filler, S.G., and Berman, J. (2002). A forkhead transcription factor is important for true hyphal growth as well as yeast morphogenesis in Candida albicans. Eukaryotic Cell 1, 787–798.

Braun, B.R., and Johnson, A.D. (1997). Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science 277, 105–109.

Braun, B.R., Kadosh, D., and Johnson, A.D. (2001). NRG1, a repressor of filamentous growth in C. albicans, is down-regulated during filament induction. EMBO J. 20, 4753–4761

Care, R.S., Trevethick, J., Binley, K.M., and Sudbery, P.E. (1999). The MET3 promotor: a new tool for Candida albicans molecular genetics. Mol. Microbiol. 34, 792–798

Chen, J., Zhou, S., Wang, Q., Chen, X., Pan, T., and Liu, H. (2000). Crk1, a novel Cdc2-related protein kinase, is required for hyphal development and virulence in Candida albicans. Mol. Cell. Biol. 20, 8596–8708.

Chen, D.C., Yang, B.C., and Kuo, T.T. (1992). One-step transformation of yeast. Curr. Genet. 21, 83–84

Cheng, L., Collyer, T., and Hardy, C.F. (1997). Cell cycle regulation of DNA replication initiator factor Dbf4p. Mol. Cell. Biol. 19, 4270–4278.

d'Enfert, C. (1997). Fungal spore germination: insights from the molecular genetics of Aspergillus nidulans and Neurospora crassa. Fungal Genet. Biol. 21, 163–172.

Ernst, J.F. (2000). Transcription factors in Candida albicans-environmental control of morphogenesis. Microbiology 146, 1763–1764

Enjalbert, B., Nantel, A., and Whiteway, M. (2003). Stress-induced gene expression in Candida albicans: absence of a general stress response. Mol. Biol. Cell 14, 1460–1467.

Fonzi, W.A., and Irwin, M.Y. (1993). Isogenic strain construction and gene mapping in Candida albicans. Genetics 134, 717–728

Gale, C., Gerami-Nejad, M., McClellan, M., Vandoninck, S., Longtine, M.S., and Berman, J. (2001). Candida albicans Int1p interacts with the septin ring in yeast and hyphal cells. Mol. Biol. Cell 12, 3538–3549

Garber, P.M., and Rine, J. (2002). Overlapping roles of the spindle assembly and DNA damage checkpoints in the cell-cycle response to altered chromosomes in Saccharomyces cerevisiae. Genetics 161, 521–534

Giusani, A.D., Vinces, M., and Kumamoto, C.A. (2002). Invasive filamentous growth of Candida albicans is promoted by Czf1p-dependent relief of Efg1p-mediated repression. Genetics 160, 1749–1753

Glover, D.M., Hagan. I.M., and Tavares, A.A.M. (1998). Polo-like kinases: a team that plays throughout mitosis. Genes Dev. 12, 3777–3787

Han, G., Liu, B., Zhang, J., Zuo, W., Morris, N.R., and Xiang, X. (2001). The Aspergillus cytoplasmic dynein heavy chain and NUDF localize to microtubule ends and affect microtubule dynamics. Curr. Biol. 11, 719–724

Hardy, C.F., and Pautz, A. (1996). A novel role for Cdc5 in DNA replication. Mol. Cell. Biol. 16, 6775–6782

Harris, S.D., Hamer. L., Sharpless, K.E., and Hamer, J.E. (1997). The Aspergillus nidulans sepA gene encodes an FH1/2 protein involved in cytokinesis and the maintenance of cellular polarity. EMBO J. 16, 3474–3483

Hazan, I., Sepulveda-Becerra, M., and Liu, H. (2002). Hyphal elongation is regulated independently of cell cycle in Candida albicans. Mol. Biol. Cell 13, 134–145

Hu, F., Wang, Y., Liu, D., Li, Y., Qin, J., and Elledge, S.J. (2001). Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell 107, 655–665

Jimenez, J., Cid, V.J., Cenamor, R., Yuste, M., Molero, G., Nombela, C., and Sanchez, M. (1998). Morphogenesis beyond cytokinetic arrest in Saccharomyces cerevisiae. J. Cell Biol. 143, 1617–1634

Kaminskyj, S.G.W., and Hamer. J.E. (1998). hyp loci control cell pattern formation in vegetative mycelium of Aspergillus nidulans. Genetics 148, 669–680

Kitada, K., Johnson, A.L., Johnston, L.H., and Sugino, A. (1993). A multicopy suppressor gene of the Saccharomyces cerevisiae G1 cell cycle mutant gene dbf4 encodes a protein kinase and is defined as CDC5. Mol. Cell. Biol. 13, 4445–4457

Köhrer, K., and Domdey, H. (1991). Preparation of high molecular weight RNA. Methods Enzymol. 194, 398–405

Kron, S.J., and Gow, N.A.R. (1995). Budding yeast morphogenesis: signaling, cytoskeleton, and cell cycle. Curr. Opin. Cell Biol. 7, 845–855

Lane, H.A., and Nigg, E.A. (1996). Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in functional maturation of mitotic centrosomes. J. Cell Biol. 135, 1701–1713.

Lane, S., Birse, C., Zhou, S., Matson, R., and Liu, H. (2001). DNA array studies demonstrate convergent regulation of virulence factors by Cph1, Cph2, and Efg1 in Candida. J. Biol. Chem. 276, 48988–48996.

Leuker, C.E., Sonneborn, A., Delbrück, S., and Ernst, F. (1997). Sequence and promotor regulation of the PCK1 gene encoding phosphoenolpyruvate carboxykinase of the fungal pathogen Candida albicans. Gene 192, 235–240

Lew, D.J., Marini, N.J., Reed, S.I. (1992). Different G1 cyclins control the timing of cell cycle commitment in mother and daughter cells of the budding yeast S. cerevisiae. Cell 69, 317–327

Lew, D.J., and Reed, S.I. (1995). A cell cycle checkpoint monitors cell morphogenesis in budding yeast. J. Cell Biol. 129, 739–749

Liu, H. (2001). Transcriptional control of dimorphism in Candida albicans. Curr. Opin. Microbiol. 4, 728–735

Llamazares, S., Moreira, A., Tavares, A., Girdham, C., Spruce, B.A., Gonzales, C., Karess, R.E., Glover, D.M., and Sunkel, C.E. (1991). polo encodes a protein kinase homolog required for mitosis in Drosophila. Genes Dev. 5, 2153–2165.

Lo, H., Köhler, J.R., DiDomenico, B., Loebnberg, D., Cacciapuoti, A., and Fink, G.R. (1997). Nonfilamentous C. albicans mutants are avirulent. Cell 90, 939–949

Loeb, J.D.J., Sepulveda-Becerra, M., Hazan, I., and Liu, H. (1999). A G1 cyclin is necessary for maintenance of filamentous growth in Candida albicans. Mol. Cell. Biol. 19, 4019–4027

Marot-Leblond, A., Grimaud, L., Nail, S., Bouterige, S., Apaire-Marchais, V., Sullivan, D.J., and Robert, R. (2000). New monoclonal antibody specific for Candida albicans germ tube. J. Clin. Microbiol. 38, 61–67

Momany, M., Westfall. P., and Abramowsky, G. (1999). Aspergillus nidulans swo mutants show defects in polarity establishment, polarity maintenance, and hyphal morphogenesis. Genetics 151, 557–567

Morschhauser, J., Michel, S., and Hacker, J. (1998). Expression of a chromasomally integrated single copy GFP gene in Candida albicans and its use as a reporter of gene regulation. Mol. Gen. Genet. 257, 412–420

Munir, A. et al. (2001). NRG1 represses yeast-hypha morphogenesis and hypha specific gene expression in Candida albicans. EMBO J. 20, 4742–4752

Nantel A. et al. (2002). Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition. Mol. Biol. Cell. 13, 3452–65

Nigg, E.A. (1998). Polo-like kinases: positive regulators of cell division from start to finish. Curr. Opin. Cell Biol. 10, 776–783

Negrado, A., Gil. C., Pla, J., and Nombela, C. (1997). Cloning analysis and one step disruption of the ARG5,6 gene of Candida albicans. Microbiology 143, 297–302

Okhura, H., Hagan, I.M., and Glover, D.M. (1995). The conserved Schizosaccharomyces pombe kinase plo1, required to form a bipolar spindle, the actin ring, and septum, can drive septum formation in G1 and G2 cells. Genes Dev. 9, 1059–1073

Rocha, C.R., Schroppel, K., Harcus, D., Marcil, A., Dignard, D., Taylor, B.N., Thomas, D.Y., Whiteway, M., and Leberer, E. (2001). Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans. Mol. Biol. Cell 12, 3631–3643

Rose, M.D., Winston, F., and Hieter, P. (1990). Methods in Yeast Genetics: A Laboratory Course Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Rua, D., Tobe, B., and Kron, S.J. (2001). Cell cycle control of yeast filamentous growth. Curr. Opin. Microbiol. 4, 720–727

Sanchez, Y., Bachant, J., Wang, H., Hu, F., Liu, D., Tetzlaff, M., and Elledge, S.J. (1999). Control of the DNA damage checkpoint by Chk1 and Rad53 protein kinases through distinct mechanisms. Science 286, 1166–1171

Sanyal, A., and Carbon, J. (2002). The CENP-A homolog CaCse4p in the pathogenic yeast Candida albicans is a centromere protein essential for chromosome transmission. Proc. Natl. Acad. Sci. USA 99, 12969–12974

Sharkey, L.L., McNemar, M.D., Saporito-Irwin, S.M., Sypherd, P.S., and Fonzi, W.A. (1999). HWP1 functions in the morphological development of Candida albicans downstream of EFG1, TUP1, and RBF1. J. Bacteriol. 181, 5273–5279

Shirayama, M., Zachariae, W., Ciosk, R. Nasmyth, K. 1998. The polo-like kinase cdc5p and the WD repeat protein Cdc20/fizzy are regulators and substrates of the anaphase-promoting complex in Saccharomyces cerevisiae. EMBO J. 17, 1336–1349

Smits, V.A.J., Klommaker, R., Arnaud, L., Rijksen, G., Nigg, E.A., and Medema, R.H. (2000). Polo-like kinase is a target of the DNA damage checkpoint. Nat. Cell Biol. 2, 672–676

Song, S., Grenfall, T.Z., Garfield, S., Erikson, R.L., and Lee, K.S. (2000). Essential function of the polo box of Cdc5 in subcellular localization and induction of cytokinetic structures. Mol. Cell. Biol. 20, 286–298

Song, S., and Lee, K.S. (2001). A novel function of Saccharomyces cerevisiae CDC5 in cytokinesis. J. Cell Biol. 152, 451–469.

Srikantha, T., and Soll, D.R. (1993). A white-specific gene in the white-opaque switching system of Candida albicans. Gene 131, 53–60

Sudbery, P.E. (2001). The germ tubes of Candida albicans hyphae and pseudohyphae show different patterns of septin ring localization. Mol. Microbiol. 41, 19–31

Torralba, S., and Heath, IB. (2001). Cytoskeletal and Ca2+ regulation of hyphal tip growth and initiation. Curr. Top. Dev. Biol. 51, 135–187

Toyoshima-Morimoto, F., Taniguchi, E., Shinya, N., Iwanatsu, A., and Nishida, E. (2001). Polo-like kinase 1 phosphorylates cyclin B and targets it to the nucleus during prophase. Nature 410, 215–220

Ushinsky, S.C., Harcus, D., Ash, J., Dignard, D., Marcil. A., Morchhauser, J., Thomas, D.Y., Whiteway, M., and Leberer, E. (2002). CDC42 is required for polarized growth in human pathogen Candida albicans. Eukaryotic Cell 1, 95–104

Whiteway, M. (2000). Transcriptional control of cell type and morphogenesis in Candida albicans. Curr. Opin. Microbiol. 3, 582–588

Winey, M., and O'Toole, E.T. (2001). The spindle cycle in budding yeast. Nat. Cell Biol. 3, E23–E27

Yokoyama, K., Kaji, H., Nishimura, K., and Miyaji, M. (1990). The role of microfilaments and microtubules in apical growth and dimorphism of Candida albicans. J. Gen. Microbiol. 136, 1067–1075
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