<i>SST2</i>
            , a Regulator of G-Protein Signaling for the
            <i>Candida albicans</i>
            Mating Response Pathway

Dignard, Daniel; Whiteway, Malcolm

doi:10.1128/ec.5.1.192-202.2006

Cited by 33 publications

(57 citation statements)

References 40 publications

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“…5A). Deleting SST2, a GTPase-activating protein, renders both S. cerevisiae and C. albicans more sensitive to the effects of ␣-factor (13,19). We therefore knocked out SST2 in an MTLa isolate of C. parapsilosis, generating strain LHS1 (see Fig.…”

Section: Analysis Of the Mating Signal Transduction Pathway In Cmentioning

confidence: 99%

Evolution of Mating within the Candida parapsilosis Species Group

et al. 2011

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Candida orthopsilosis and Candida metapsilosis are closely related to Candida parapsilosis, a major cause of infection in premature neonates. Mating has not been observed in these species. We show that ϳ190 isolates of C. parapsilosis contain only an MTLa idiomorph at the mating-type-like locus. Here, we describe the isolation and characterization of the MTL loci from C. orthopsilosis and C. metapsilosis. Among 16 C. orthopsilosis isolates, 9 were homozygous for MTLa, 5 were homozygous for MTL␣, and 2 were MTLa/␣ heterozygotes. The C. orthopsilosis isolates belonged to two divergent groups, as characterized by restriction patterns at MTL, which probably represent subspecies. We sequenced both idiomorphs from each group and showed that they are 95% identical and that the regulatory genes are intact. In contrast, 18 isolates of C. metapsilosis contain only MTL␣ idiomorphs. Our results suggest that the role of MTL in determining cell type is being eroded in the C. parapsilosis species complex. The population structure of C. orthopsilosis indicates that mating may occur. However, expression of genes in the mating signal transduction pathway does not respond to exposure to alpha factor. C. parapsilosis is also nonresponsive, even when the GTPase-activating protein gene SST2 is deleted. In addition, splicing of introns in MTLa1 and MTLa2 is defective in C. orthopsilosis. Mating is not detected. The alpha factor peptide, which is the same sequence in C. parapsilosis, C. orthopsilosis, and C. metapsilosis, can induce a mating response in Candida albicans. It is therefore likely either that mating of C. orthopsilosis takes place under certain unidentified conditions or that the mating pathway has been adapted for other functions, such as cross-species communication.

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Section: Analysis Of the Mating Signal Transduction Pathway In Cmentioning

confidence: 99%

Evolution of Mating within the Candida parapsilosis Species Group

et al. 2011

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“…If the tested strain can secrete, either constitutively or in response to pheromone, a protein with pheromone-degrading activity, then it will generate a barrier to the diffusion of a source of alpha pheromone placed next to it, and the lawn of sensitive cells on the other side of this barrier will be able to grow. We tested barrier activity in a wild-type strain (3294) and in the super-pheromone-sensitive ⌬sst2 strain (Ca29) (10). As shown in Fig.…”

Section: Schaefer Et Al Eukaryot Cellmentioning

confidence: 99%

“…Under optimal medium conditions, the pheromone response of opaque cells of C. albicans involves the differential regulation of more than 200 genes, and relatively few of these genes overlap with those regulated by pheromone in S. cerevisiae (3). Even under optimal conditions, however, wild-type C. albicans cells fail to undergo complete cell cycle arrest in the presence of pheromone (3,10,41). In contrast, S. cerevisiae cells responding to pheromone efficiently arrest their growth in the G 1 phase of the cell cycle, and this is often visualized by the formation of halos of growth inhibition in a lawn of responding cells (35).…”

mentioning

confidence: 99%

“…C. albicans strains do not exhibit clear areas of growth inhibition in the halo assay, although mutant strains that are hypersensitive to pheromone can produce halos, demonstrating more efficient cell cycle arrest. An example of a hypersensitive C. albicans strain is one lacking the SST2 gene, which encodes a regulator of G protein signaling (10). Disruption of SST2 resulted in heightened signaling via the MAP kinase cascade, and opaque a cells exhibited increased sensitivity to alpha pheromone and enhanced growth inhibition in the halo assay.…”

mentioning

confidence: 99%

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Barrier Activity in Candida albicans Mediates Pheromone Degradation and Promotes Mating

Schaefer

Côté²,

Whiteway³

et al. 2007

Eukaryot Cell

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Mating in Candida albicans and Saccharomyces cerevisiae is regulated by the secretion of peptide pheromones that initiate the mating process. An important regulator of pheromone activity in S. cerevisiae is barrier activity, involving an extracellular aspartyl protease encoded by the BAR1 gene that degrades the alpha pheromone. We have characterized an equivalent barrier activity in C. albicans and demonstrate that the loss of C. albicans BAR1 activity results in opaque a cells exhibiting hypersensitivity to alpha pheromone. Hypersensitivity to pheromone is clearly seen in halo assays; in response to alpha pheromone, a lawn of C. albicans ⌬bar1 mutant cells produces a marked zone in which cell growth is inhibited, whereas wild-type strains fail to show halo formation. C. albicans mutants lacking BAR1 also exhibit a striking mating defect in a cells, but not in ␣ cells, due to overstimulation of the response to alpha pheromone. The block to mating occurs prior to cell fusion, as very few mating zygotes were observed in mixes of ⌬bar1 a and ␣ cells. Finally, in a barrier assay using a highly pheromone-sensitive strain, we were able to demonstrate that barrier activity in C. albicans is dependent on Bar1p. These studies reveal that a barrier activity to alpha pheromone exists in C. albicans and that the activity is analogous to that caused by Bar1p in S. cerevisiae.Candida albicans a and ␣ cells secrete peptide mating pheromones (a-factor and ␣-factor, respectively) that act on cells of the opposite mating type and induce physiological changes that precede cell fusion (4,9,29,36,41). These changes include arrest of the cell in the G 1 phase of the cell cycle and the formation of mating projections that seek out a partner of the opposite mating type for cell fusion (3, 52). The pathway controlling the response to mating pheromones in C. albicans shows many similarities with that of the related yeast Saccharomyces cerevisiae.

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“…Patch mating experiments, using auxotrophic marker complementation with strain 3315 as the MTL␣ tester strain, were done as described previously (31). Briefly, all the assayed strains were maintained in the opaque phase at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Ste18p Is a Positive Control Element in the Mating Process of Candida albicans

Sun

Jiang

et al. 2014

Eukaryot Cell

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bHeterotrimeric G proteins are an important class of eukaryotic signaling molecules that have been identified as central elements in the pheromone response pathways of many fungi. In the fungal pathogen Candida albicans, the STE18 gene (ORF19.6551.1) encodes a potential ␥ subunit of a heterotrimeric G protein; this protein contains the C-terminal CAAX box characteristic of ␥ subunits and has sequence similarity to ␥ subunits implicated in the mating pathways of a variety of fungi. Disruption of this gene was shown to cause sterility of MTLa mating cells and to block pheromone-induced gene expression and shmoo formation; deletion of just the CAAX box residues is sufficient to inactivate Ste18 function in the mating process. Intriguingly, ectopic expression behind the strong ACT1 promoter of either the G␣ or the G␤ subunit of the heterotrimeric G protein is able to suppress the mating defect caused by deletion of the G␥ subunit and restore both pheromone-induced gene expression and morphology changes.

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SST2 , a Regulator of G-Protein Signaling for the Candida albicans Mating Response Pathway

Cited by 33 publications

References 40 publications

Evolution of Mating within the Candida parapsilosis Species Group

Evolution of Mating within the Candida parapsilosis Species Group

Barrier Activity in Candida albicans Mediates Pheromone Degradation and Promotes Mating

Ste18p Is a Positive Control Element in the Mating Process of Candida albicans

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