Protein kinase A encoded by <i>TPK2</i> regulates dimorphism of <i>Candida albicans</i>

Sonneborn, Anja; Bockmühl, Dirk P.; Gerads, Michaela; Kurpanek, Katharina; Sanglard, Dominique; Ernst, Joachim F.

doi:10.1046/j.1365-2958.2000.01705.x

Cited by 187 publications

(230 citation statements)

References 42 publications

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“…On the other hand, the ligand-binding mutants, Ud-K51E and Ud-L231S, were hyperfilamentous with very sparse, if any, production of chlamydospores. This phenotype is very similar to that described for the efg1/efg1 and phosphorylation EFG1(T206A) mutants (Sonneborn et al, 1999). Other pathways and genes have been implicated in chlamydospore formation, including the Hog1 oxidative stress response and alkaline pH response pathways (Alonso-Monge et al, 2003;Nobile et al, 2003).…”

Section: Discussionsupporting

confidence: 80%

Mutant alleles of the essential 14-3-3 gene in Candida albicans distinguish between growth and filamentation

et al. 2004

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The opportunistic fungal pathogen Candida albicans has the ability to exploit diverse host environments and can either reside commensally or cause disease. In order to adapt to its new environment it must respond to new physical conditions, nutrient sources, and the host immune response. This requires the co-regulation of multiple signalling networks. The 14-3-3 family of proteins is highly conserved in all eukaryotic species. These proteins regulate signalling pathways involved in cell survival, the cell cycle, and differentiation, and effect their functions via interactions with phosphorylated serines/threonines. In C. albicans there is only one 14-3-3 protein, Bmh1p, and it is required for vegetative growth and optimal filamentation. In order to dissect separate functions of Bmh1p in C. albicans, site-directed nucleotide substitutions were made in the C. albicans BMH1 gene based on studies in other species. Putative temperature-sensitive, ligand-binding and dimerization mutants were constructed. In addition two mutant strains identified through random mutagenesis were analysed. All five mutant strains demonstrated varying defects in growth and filamentation. This paper begins to segregate functions of Bmh1p that are required for optimal growth and the different filamentation pathways. These mutant strains will allow the identification of 14-3-3 target interactions and correlate the individual functions of Bmh1p to cellular processes involved in pathogenesis.

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Section: Discussionsupporting

confidence: 80%

Mutant alleles of the essential 14-3-3 gene in Candida albicans distinguish between growth and filamentation

et al. 2004

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“…Supernatants were neutralized by five washes Miscellaneous. For overexpression of EFG, the plasmid pBI-HAHYD, containing EFG1 under the control of the PCK1 promoter (Sonneborn et al, 2000) was transformed into WH2-4 (Table 4) and three transformants were tested. An Axiovert 200 (Zeiss) microscope equipped with a CoolSNAP HQ camera was used for observation of cell morphology in liquid medium at 6630 magnification.…”

Section: Methodsmentioning

confidence: 99%

“…The exact pattern of cAMP changes still remains an unresolved issue, regardless of the fact that several components of the cAMP-dependent pathway have recently been characterized in C. albicans. The PKA isoforms Tpk1p and Tpk2p have both distinct and redundant roles in morphogenesis and growth (Sonneborn et al, 2000;Bockmühl et al, 2001). The adenylate cyclase CaCdc35p is essential for hyphal growth and virulence (Rocha et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans

Jung

Stateva

2003

Microbiology

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The cAMP-dependent pathway, which regulates yeast-to-hypha morphogenesis in Candida albicans, is controlled by changes in cAMP levels determined by the processes of synthesis and hydrolysis. Both low-and high-affinity cAMP phosphodiesterases are encoded in the C. albicans genome. CaPDE2, encoding the high-affinity cAMP phosphodiesterase, has been cloned and shown to be toxic in Saccharomyces cerevisiae upon overexpression under pGAL1, but functional under the moderate pMET3. Deletion of CaPDE2 causes elevated cAMP levels and responsiveness to exogenous cAMP, higher sensitivity to heat shock, severe growth defects at 42 6C and highly reduced levels of EFG1 transcription. In vitro in hypha-inducing liquid medium CaPDE2, deletion prohibits normal hyphal, but not pseudohyphal growth. On solid medium capde2 mutants form aberrant hyphae, with fewer branches and almost no lateral buds, which are deficient in hypha-to-yeast reversion. The phenotypic defects of capde2 mutants show that the cAMP-dependent pathway plays specific roles in hyphal and pseudohyphal development, its regulatory role however, being greater in liquid than on solid medium in vitro. The increased expression of CaPDE2 after serum addition correlates well with a drop in cAMP levels following the initial rise in response to the hyphal inducer. These results suggest that Capde2p mediates a desensitization mechanism by lowering basal cAMP levels in response to environmental stimuli in C. albicans.

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“…The G proteins act through PKA to induce morphogenesis in C. albicans. C. albicans PKA consists of one regulatory subunit, Bcy1, and two catalytic subunits, Tpk1 and Tpk2 (Sonneborn et al, 2000;Bockmuhl et al, 2001;Cassola et al, 2004). Tpk1 and Tpk2 have distinct functions in hyphal development because their mutants have differential effects in different media (Bockmuhl et al, 2001;Cassola et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence inCandida albicans

Cao

Lane

Raniga

et al. 2006

MBoC

198

255

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The transcription factor Flo8 is essential for filamentous growth in Saccharomyces cerevisiae and is regulated under the cAMP/protein kinase A (PKA) pathway. To determine whether a similar pathway/regulation exists in Candida albicans, we have cloned C. albicans FLO8 by its ability to complement S. cerevisiae flo8. Deleting FLO8 in C. albicans blocked hyphal development and hypha-specific gene expression. The flo8/flo8 mutant is avirulent in a mouse model of systemic infection. Genome-wide transcription profiling of efg1/efg1 and flo8/flo8 using a C. albicans DNA microarray suggests that Flo8 controls subsets of Efg1-regulated genes. Most of these genes are hypha specific, including HGC1 and IHD1. We also show that Flo8 interacts with Efg1 in yeast and hyphal cells by in vivo immunoprecipitation. Similar to efg1/efg1, flo8/flo8 and cdc35/cdc35 show enhanced hyphal growth under an embedded growth condition. Our results suggest that Flo8 may function downstream of the cAMP/PKA pathway, and together with Efg1, regulates the expression of hypha-specific genes and genes that are important for the virulence of C. albicans.

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Protein kinase A encoded by TPK2 regulates dimorphism of Candida albicans

Cited by 187 publications

References 42 publications

Mutant alleles of the essential 14-3-3 gene in Candida albicans distinguish between growth and filamentation

Mutant alleles of the essential 14-3-3 gene in Candida albicans distinguish between growth and filamentation

The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans

The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence inCandida albicans

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