scholarly journals Temporal and Spatial Control of HGC1 Expression Results in Hgc1 Localization to the Apical Cells of Hyphae in Candida albicans

2006 ◽  
Vol 6 (2) ◽  
pp. 253-261 ◽  
Author(s):  
Allen Wang ◽  
Shelley Lane ◽  
Zhen Tian ◽  
Amir Sharon ◽  
Idit Hazan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Protein Turnover ◽  
Growth Form ◽  
Apical Cell ◽  
Hyphal Growth ◽  
Independent Manner ◽  
Spatial Control ◽  
Apical Cells ◽  
Temporal And Spatial

ABSTRACT The human fungal pathogen Candida albicans can undergo a morphological transition from a unicellular yeast growth form to a multicellular hyphal growth form. During hyphal growth, cell division is asymmetric. Only the apical cell divides, whereas subapical cells remain in G1, and cell surface growth is highly restricted to the tip of the apical cell. Hgc1, a hypha-specific, G1 cyclin-like protein, is essential for hyphal development. Here, we report, using indirect immunofluorescence, that Hgc1 is preferentially localized to the dividing apical cells of hyphae. Hgc1 protein is rapidly degraded in a cell cycle-independent manner, and the protein turnover likely occurs in both the apical and the subapical cells of hyphae. In addition to rapid protein turnover, the HGC1 transcript is also dynamically regulated during cell cycle progression in hyphal growth. It is induced upon germ tube formation in early G1; the transcript level is reduced during the G1/S transition and peaks again around the G2/M phase in the subsequent cell cycles. Transcription from the HGC1 promoter is essential for its apical cell localization, as Hgc1 no longer exhibits preferential apical localization when expressed under the MAL2 promoter. Using fluorescence in situ hybridization, the HGC1 transcript is detected only in the apical cells of hyphae, suggesting that HGC1 is transcribed in the apical cell. Therefore, the preferential localization of Hgc1 to the apical cells of hyphae results from the dynamic temporal and spatial control of HGC1 expression.

scholarly journals Cell Cycle-Independent Phospho-Regulation of Fkh2 during Hyphal Growth Regulates Candida albicans Pathogenesis

2015 ◽  
Vol 11 (1) ◽  
pp. e1004630 ◽  
Author(s):  
Jamie A. Greig ◽  
Ian M. Sudbery ◽  
Jonathan P. Richardson ◽  
Julian R. Naglik ◽  
Yue Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Hyphal Growth

scholarly journals Candida albicans Rho-Type GTPase-Encoding Genes Required for Polarized Cell Growth and Cell Separation

2007 ◽  
Vol 6 (5) ◽  
pp. 844-854 ◽  
Author(s):  
Alexander Dünkler ◽  
Jürgen Wendland
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Cell Polarity ◽  
Cell Separation ◽  
Cycle Length ◽  
Hyphal Growth ◽  
Rho Proteins ◽  
Polarized Cell Growth ◽  
Bud Growth ◽  
Cell Cycle Length

ABSTRACT Rho proteins are essential regulators of morphogenesis in eukaryotic cells. In this report, we investigate the role of two previously uncharacterized Rho proteins, encoded by the Candida albicans RHO3 (CaRHO3) and CaCRL1/CaRHO4 genes. The CaRHO3 gene was found to contain one intron. Promoter shutdown experiments using a MET3 promoter-controlled RHO3 revealed a strong cell polarity defect and a partially depolarized actin cytoskeleton. Hyphal growth after promoter shutdown was abolished in rho3 mutants even in the presence of a constitutively active ras1(G13V) allele, and existing germ tubes became swollen. Deletion of C. albicans RHO4 indicated that it is a nonessential gene and that rho4 mutants were phenotypically different from rho3. Two distinct phenotypes of rho4 cells were elongated cell morphology and an unexpected cell separation defect generating chains of cells. Colony morphology of crl1/rho4 resulted in a growth-dependent smooth (long cell cycle length) or wrinkled (short cell cycle length) phenotype. This phenotype was additionally dependent on the rho4 cell separation defect and was also found in a Cacht3 chitinase mutant that shows a strong cytokinesis defect. The overexpression of the endoglucanase encoding the ENG1 gene, but not CHT3, suppressed the cell separation defect of crl1/rho4 but could not suppress the cell elongation phenotype. C. albicans Crl1/Rho4 and Bnr1 both localize to septal sites in yeast and hyphal cells but not to the hyphal tip. Deletion of RHO4 and BNR1 produced similar morphological phenotypes. Based on the localization of Rho4 and on the rho4 mutant phenotype, we propose a model in which Rho4p may function as a regulator of cell polarity, breaking the initial axis of polarity found during early bud growth to promote the construction of a septum.

A putative dual-specific protein phosphatase encoded by YVH1 controls growth, filamentation and virulence in Candida albicans

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2223-2232 ◽  
Author(s):  
Nozomu Hanaoka ◽  
Takashi Umeyama ◽  
Keigo Ueno ◽  
Kenji Ueda ◽  
Teruhiko Beppu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Cell Cycle Progression ◽  
Germ Tube ◽  
Hyphal Growth ◽  
Tube Formation ◽  
Yeast Cells ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Cycle Progression

In response to stimulants, such as serum, the yeast cells of the opportunistic fungal pathogen Candida albicans form germ tubes, which develop into hyphae. Yvh1p, one of the 29 protein phosphatases encoded in the C. albicans genome, has 45 % identity with the dual-specific phosphatase Yvh1p of the model yeast Saccharomyces cerevisiae. In this study, Yvh1p expression was not observed during the initial step of germ tube formation, although Yvh1p was expressed constitutively in cell cycle progression of yeast or hyphal cells. In an attempt to analyse the function of Yvh1p phosphatase, the complete ORFs of both alleles were deleted by replacement with hph200–URA3–hph200 and ARG4. Although YVH1 has nine single-nucleotide polymorphisms in its coding sequence, both YVH1 alleles were able to complement the YVH1 gene disruptant. The vegetative growth of Δyvh1 was significantly slower than the wild-type. The hyphal growth of Δyvh1 on agar, or in a liquid medium, was also slower than the wild-type because of the delay in nuclear division and septum formation, although germ tube formation was similar between the wild-type and the disruptant. Despite the slow hyphal growth, the expression of several hypha-specific genes in Δyvh1 was not delayed or repressed compared with that of the wild-type. Infection studies using mouse models revealed that the virulence of Δyvh1 was less than that of the wild-type. Thus, YVH1 contributes to normal vegetative yeast or hyphal cell cycle progression and pathogenicity, but not to germ tube formation.

scholarly journals PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis.

1995 ◽  
Vol 15 (2) ◽  
pp. 601-613 ◽  
Author(s):  
S M Saporito-Irwin ◽  
C E Birse ◽  
P S Sypherd ◽  
W A Fonzi
Keyword(s):  
Candida Albicans ◽  
Apical Cell ◽  
Protein A ◽  
Surface Protein ◽  
Hyphal Growth ◽  
Morphological Plasticity ◽  
Opportunistic Pathogen ◽  
Predicted Amino Acid Sequence ◽  
Alkaline Ph ◽  
Environmental Signals

Candida albicans, like many fungi, exhibits morphological plasticity, a property which may be related to its biological capacity as an opportunistic pathogen of humans. Morphogenesis and alterations in cell shape require integration of many cellular functions and occur in response to environmental signals, most notably pH and temperature in the case of C. albicans. In the course of our studies of differential gene expression associated with dimorphism of C. albicans, we have isolated a gene, designated PHR1, which is regulated in response to the pH of the culture medium. PHR1 expression was repressed at pH values below 5.5 and induced at more alkaline pH. The predicted amino acid sequence of the PHR1 protein was 56% identical to that of the Saccharomyces cerevisiae Ggp1/Gas1 protein, a highly glycosylated cell surface protein attached to the membrane via glycosylphosphatidylinositol. A homozygous null mutant of PHR1 was constructed and found to exhibit a pH-conditional morphological defect. At alkaline pH, the mutant, unlike the parental type, was unable to conduct apical growth of either yeast or hyphal growth forms. This morphological aberration was not associated with defective cytoskeletal polarization or secretion. The results suggest that PHR1 defines a novel function required for apical cell growth and morphogenesis.

scholarly journals Cyclin Cln3p Links G1 Progression to Hyphal and Pseudohyphal Development in Candida albicans

2005 ◽  
Vol 4 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Catherine Bachewich ◽  
Malcolm Whiteway
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Critical Role ◽  
Growth Conditions ◽  
Yeast Cells ◽  
Independent Manner ◽  
Cell Cycles ◽  
Environmental Controls ◽  
A Cell ◽  
Synthetically Lethal

ABSTRACT G1 cyclins coordinate environmental conditions with growth and differentiation in many organisms. In the pathogen Candida albicans, differentiation of hyphae is induced by environmental cues but in a cell cycle-independent manner. Intriguingly, repressing the G1 cyclin Cln3p under yeast growth conditions caused yeast cells to arrest in G1, increase in size, and then develop into hyphae and pseudohyphae, which subsequently resumed the cell cycle. Differentiation was dependent on Efg1p, Cph1p, and Ras1p, but absence of Ras1p was also synthetically lethal with repression of CLN3. In contrast, repressing CLN3 in environment-induced hyphae did not inhibit growth or the cell cycle, suggesting that yeast and hyphal cell cycles may be regulated differently. Therefore, absence of a G1 cyclin can activate developmental pathways in C. albicans and uncouple differentiation from the normal environmental controls. The data suggest that the G1 phase of the cell cycle may therefore play a critical role in regulating hyphal and pseudohyphal development in C. albicans.

scholarly journals A Forkhead Transcription Factor Is Important for True Hyphal as well as Yeast Morphogenesis in Candida albicans

2002 ◽  
Vol 1 (5) ◽  
pp. 787-798 ◽  
Author(s):  
Eric S. Bensen ◽  
Scott G. Filler ◽  
Judith Berman
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Yeast Cells ◽  
Cycle Progression ◽  
Forkhead Transcription Factors

ABSTRACT Candida albicans is an important pathogen of immunocompromised patients which grows with true hyphal, pseudohyphal, and yeast morphologies. The dynamics of cell cycle progression are markedly different in true hyphal relative to pseudohyphal and yeast cells, including nuclear movement and septin ring positioning. In Saccharomyces cerevisiae, two forkhead transcription factors (ScFKH1 and ScFKH2) regulate the expression of B-cyclin genes. In both S. cerevisiae and Schizosaccharomyces pombe, forkhead transcription factors also influence morphogenesis. To explore the molecular mechanisms that connect C. albicans morphogenesis with cell cycle progression, we analyzed CaFKH2, the single homolog of S. cerevisiae FKH1/FKH2. C. albicans cells lacking CaFkh2p formed constitutive pseudohyphae under all yeast and hyphal growth conditions tested. Under hyphal growth conditions levels of hyphae-specific mRNAs were reduced, and under yeast growth conditions levels of several genes encoding proteins likely to be important for cell wall separation were reduced. Together these results imply that Fkh2p is required for the morphogenesis of true hyphal as well as yeast cells. Efg1p and Cph1p, two transcription factors that contribute to C. albicans hyphal growth, were not required for the pseudohyphal morphology of fkh2 mutants, implying that Fkh2p acts in pathways downstream of and/or parallel to Efg1p and Cph1p. In addition, cells lacking Fkh2p were unable to damage human epithelial or endothelial cells in vitro, suggesting that Fkh2p contributes to C. albicans virulence.

scholarly journals A G1 Cyclin Is Necessary for Maintenance of Filamentous Growth in Candida albicans

1999 ◽  
Vol 19 (6) ◽  
pp. 4019-4027 ◽  
Author(s):  
Jonathan D. J. Loeb ◽  
Marisa Sepulveda-Becerra ◽  
Idit Hazan ◽  
Haoping Liu
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Cell Cycle Progression ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Specific Expression ◽  
Molecular Control ◽  
Solid Media ◽  
Specific Expression Pattern ◽  
Germ Tubes

ABSTRACT Candida albicans undergoes a dramatic morphological transition in response to various growth conditions. This ability to switch from a yeast form to a hyphal form is required for its pathogenicity. The intractability of Candida to traditional genetic approaches has hampered the study of the molecular mechanism governing this developmental switch. Our approach is to use the more genetically tractable yeast Saccharomyces cerevisiae to yield clues about the molecular control of filamentation for further studies in Candida. G1 cyclins Cln1 and Cln2 have been implicated in the control of morphogenesis in S. cerevisiae. We show that C. albicans CLN1(CaCLN1) has the same cell cycle-specific expression pattern as CLN1 and CLN2 of S. cerevisiae. To investigate whether G1 cyclins are similarly involved in the regulation of cell morphogenesis during the yeast-to-hypha transition of C. albicans, we mutatedCaCLN1. Cacln1/Cacln1 cells were found to be slower than wild-type cells in cell cycle progression. TheCacln1/Cacln1 mutants were also defective in hyphal colony formation on several solid media. Furthermore, while mutant strains developed germ tubes under several hypha-inducing conditions, they were unable to maintain the hyphal growth mode in a synthetic hypha-inducing liquid medium and were deficient in the expression of hypha-specific genes in this medium. Our results suggest that CaCln1 may coordinately regulate hyphal development with signal transduction pathways in response to various environmental cues.

scholarly journals Asynchronous Cell Cycle and Asymmetric Vacuolar Inheritance in True Hyphae of Candida albicans

2003 ◽  
Vol 2 (3) ◽  
pp. 398-410 ◽  
Author(s):  
Caroline J. Barelle ◽  
Erin A. Bohula ◽  
Stephen J. Kron ◽  
Deborah Wessels ◽  
David R. Soll ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Cell Cycle Arrest ◽  
Imaging System ◽  
Apical Cell ◽  
Continuous Extension ◽  
Time Lapse ◽  
Cell Types ◽  
Eukaryotic Cell ◽  
Cycle Arrest

ABSTRACT Candida albicans forms unconstricted hyphae in serum-containing medium that are divided into discrete compartments. Time-lapse photomicroscopy, flow cytometry, and a novel three-dimensional imaging system were used to demonstrate that the kinetics and cell cycle events accompanying hyphal development were correlated with dynamic changes in vacuole morphology and the pattern of vacuole inheritance. Apical cells of hyphae underwent continuous extension before and after the first cytokinesis event. However, the resulting mother cell and sub-apical compartments did not immediately reenter the cell cycle and instead underwent cell cycle arrest before reentering the cycle. Vacuole was inherited asymmetrically at cytokinesis so that the distal, arrested compartments inherited most vacuole and the growing apical cell inherited most cytoplasm. Hydroxyurea release experiments demonstrated that the arrested, vacuolated hyphal compartments were in the G1 phase of the cycle. The period of cell cycle arrest was decreased by the provision of assimilatable forms of nitrogen, suggesting that the hyphal cell cycle is regulated by nitrogen limitation that results in sup-apical cell cycle arrest. This pattern of growth is distinct from that of the synchronous, symmetrical development of pseudohyphae of C. albicans and other yeast species. These observations suggest that the cellular vacuole space correlates with alterations in the cell cycles of different cell types and that the total organelle space may influence size-regulated functions and hence the timing of the eukaryotic cell cycle.

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