TheCandida albicans PKC1 gene encodes a protein kinase C homolog necessary for cellular integrity but not dimorphism

Paravicini, Gerhard; Mendoza, A. Hermoso de; Antonsson, Bruno; Cooper, Michelle; Losberger, Christophe; Payton, Mark

doi:10.1002/(sici)1097-0061(19960630)12:8<741::aid-yea967>3.0.co;2-g

Cited by 78 publications

(39 citation statements)

References 78 publications

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“…3B) by Northern blotting required long exposure times. Low mRNA levels were consistent with unbiased codon usage in that the effective number of codons (83), 43.1, was typical of genes that are expressed at low levels, such as those for protein kinase C (PKC1) (64) and MAPK (MKC1) (60), with values of 45 and 54.8, respectively.…”

Section: Vol 183 2001mentioning

confidence: 84%

CAP1 , an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans

2001

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In response to a wide variety of environmental stimuli, the opportunistic fungal pathogen Candida albicans exits the budding cycle, producing germ tubes and hyphae concomitant with expression of virulence genes, such as that encoding hyphal wall protein 1 (HWP1). Biochemical studies implicate cyclic AMP (cAMP) increases in promoting bud-hypha transitions, but genetic evidence relating genes that control cAMP levels to bud-hypha transitions has not been reported. Adenylate cyclase-associated proteins (CAPs) of nonpathogenic fungi interact with Ras and adenylate cyclase to increase cAMP levels under specific environmental conditions. To initiate studies on the relationship between cAMP signaling and bud-hypha transitions in C. albicans, we identified, cloned, characterized, and disrupted the C. albicans CAP1 gene. C. albicans strains with inactivated CAP1 budded in conditions that led to germ tube formation in isogenic strains with CAP1. The addition of 10 mM cAMP and dibutyryl cAMP promoted bud-hypha transitions and filamentous growth in the cap1/cap1 mutant in liquid and solid media, respectively, showing clearly that cAMP promotes hypha formation in C. albicans. Increases in cytoplasmic cAMP preceding germ tube emergence in strains having CAP1 were markedly diminished in the budding cap1/cap1 mutant. C. albicans strains with deletions of both alleles of CAP1 were avirulent in a mouse model of systemic candidiasis. The avirulence of a germ tube-deficient cap1/cap1 mutant coupled with the role of Cap1 in regulating cAMP levels shows that the Cap1-mediated cAMP signaling pathway is required for bud-hypha transitions, filamentous growth, and the pathogenesis of candidiasis.For many pathogenic fungi, interconversions between morphological growth forms, particularly between yeast growth and filamentous growth, coincide with adaptation to a host environment followed by tissue destruction. Morphological interconversions in fungi are dependent upon signal transduction pathways, including the cyclic AMP (cAMP)-dependent protein kinase A (PKA) pathway (8,10,28,40,46). For the plant pathogens Ustilago maydis and Magnaporthe grisea, cAMP signaling is important for the establishment of filamentous growth in the former and for formation of the infecting appressorium structure of the latter (40, 46). Knowledge about how cAMP signaling mediates morphological interconversion is best understood for Saccharomyces cerevisiae, a budding yeast that produces elongated pseudohyphal cells and forms filamentous colonies in the presence of limiting nitrogen (28, 46). Pseudohyphae exhibit unipolar budding, do not separate, and invade agar (31). Recent experiments involving gene disruption and epistasis analyses have elucidated both upstream and downstream elements of the cAMP-dependent pseudohyphal growth pathway in S. cerevisiae (28,40,46). Adenylate cyclase is activated either through a receptor (Gpr1) that is coupled to a G protein (Gpa2) or by Ras2 (31,41,52,53,58,80). The subsequent activation of PKA then results in activation of the ...

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Section: Vol 183 2001mentioning

confidence: 84%

CAP1 , an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans

2001

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“…5). A pkc1 null strain has a cell lysis defect, which is osmotically remediable; however, normal hyphal morphogenesis occurs in stabilized liquid serum media (230). The downstream target of Pkc1, the MAPK Mkc1 (homolog of yeast Slt2), is also affected in morphogenesis under certain conditions (215,217).…”

Section: Other Mapk Pathways Involved In Morphogenesismentioning

confidence: 99%

Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans

Biswas

Dijck

Datta

2007

Microbiol Mol Biol Rev

468

527

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SUMMARY Candida albicans is an opportunistic fungal pathogen that is found in the normal gastrointestinal flora of most healthy humans. However, under certain environmental conditions, it can become a life-threatening pathogen. The shift from commensal organism to pathogen is often correlated with the capacity to undergo morphogenesis. Indeed, under certain conditions, including growth at ambient temperature, the presence of serum or N-acetylglucosamine, neutral pH, and nutrient starvation, C. albicans can undergo reversible transitions from the yeast form to the mycelial form. This morphological plasticity reflects the interplay of various signal transduction pathways, either stimulating or repressing hyphal formation. In this review, we provide an overview of the different sensing and signaling pathways involved in the morphogenesis and pathogenesis of C. albicans. Where appropriate, we compare the analogous pathways/genes in Saccharomyces cerevisiae in an attempt to highlight the evolution of the different components of the two organisms. The downstream components of these pathways, some of which may be interesting antifungal targets, are also discussed.

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“…In S. cerevisiae, Pkc1p controls the cell integrity signalling pathway, being upstream of the MAP kinase module. In a similar manner to S. cerevisiae, C. albicans pkc1 mutants have been shown to be much more fragile than mkc1D mutants, as they are unable to survive in the long term without osmotic protection (Paravicini et al, 1996). In contrast to the HOG pathway, little is known about the physiological conditions that might activate Mkc1p, such as stimuli and the epistatic relationship with PKC1.…”

Section: Introductionmentioning

confidence: 99%

The MAP kinase Mkc1p is activated under different stress conditions in Candida albicans

et al. 2005

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Candida albicans is an opportunistic pathogen that has adapted to live and grow in the human body as its natural environment. Under these conditions, this fungus faces numerous challenges, including oxidative, osmotic and enzymic processes that may damage external and internal structures. In view of the key role of MAP kinase signalling pathways in the physiology of C. albicans, the effect of agents mimicking in vivo environmental conditions on the activation of the p42-44 MAP kinases has been analysed. It has been found that Mkc1p is phosphorylated in the presence of oxidative stress, changes in osmotic pressure, cell wall damage and a decrease in the growth temperature. This phosphorylation is dependent on Pkc1p, indicating that both proteins operate in the same signalling pathway in C. albicans. Under some stimuli, the phosphorylation of Mkc1p required the presence of Hog1p, the MAP kinase of the high osmolarity glycerol (HOG) pathway. This suggests the existence of a new regulatory role, at least under some conditions, for these MAP kinase pathways in yeast.

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TheCandida albicans PKC1 gene encodes a protein kinase C homolog necessary for cellular integrity but not dimorphism

Cited by 78 publications

References 78 publications

CAP1 , an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans

CAP1 , an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans

Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans

The MAP kinase Mkc1p is activated under different stress conditions in Candida albicans

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