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Ste18p is a positive control element in the mating process of Candida albicans.

ABSTRACT: Heterotrimeric 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.

SUBMITTER: Lu H

PROVIDER: S-EPMC4000101 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Ste18p is a positive control element in the mating process of Candida albicans.

Lu Hui H Sun Yuan Y Jiang Yuan-Ying YY Whiteway Malcolm M

Eukaryotic cell 20140131 4

Heterotrimeric 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 γ subunit of a heterotrimeric G protein; this protein contains the C-terminal CAAX box characteristic of γ subunits and has sequence similarity to γ subunits implicated in the mating pathways of a variety of fungi. Disruption of t ...[more]

PMID: 24489040

Similar Datasets

Ste18p is a positive control element in the mating process of Candida albicans

Project description:Disruption of STE18 gene which encodes a γ subunit of a heterotrimeric G protein in Candida albicans is shown to block pheromone-induced gene expression. Ectopic expression of either the Gα or the Gβ subunit of the heterotrimeric G protein is able to restore pheromone-induced gene expression.

2014-01-14 | GSE54031 | GEO

Ste18p is a positive control element in the mating process of Candida albicans

Project description:Disruption of STE18 gene which encodes a Î³ subunit of a heterotrimeric G protein in Candida albicans is shown to block pheromone-induced gene expression. Ectopic expression of either the GÎ± or the GÎ² subunit of the heterotrimeric G protein is able to restore pheromone-induced gene expression. The transcriptional response to pheromone treatment was measured in the wild type strain, in a strain deleted for STE18, and in STE18 deleted strains ectopic expressing either the GÎ± or the GÎ² subunit of G protein in opaque forms under RT.

2014-01-14 | E-GEOD-54031 | biostudies-arrayexpress

Cell biology of mating in Candida albicans.

Project description:It was recently demonstrated that strains homozygous for either of the mating type-like loci MTLa and MTLalpha of Candida albicans undergo white-opaque switching and that expression of the opaque-phase phenotype greatly enhances mating between strains. Exploiting the latter property to obtain high-frequency mating, we have characterized the cell biology of the mating process of C. albicans. Employing continuous videomicroscopy, computer-assisted three-dimensional reconstruction of living cells, and fluorescence microscopy, we have monitored the mating-associated processes of conjugation, tube formation, fusion, budding, septum formation, and daughter cell development and the spatial and temporal dynamics of nuclear migration and division. From these observations, a model for the stages in C. albicans mating is formulated. The stages include shmooing, chemotropism of conjugation tubes, fusion of tubes and nuclear association, vacuole expansion and nuclear separation in the conjugation bridge, asynchronous nuclear division in the zygote, bud growth, nuclear migration into the daughter cell, septation, and daughter cell budding. Since there was no cytological indication of karyogamy, genetic experiments were performed to assess marker segregation. Recombination was not observed, suggesting that mating takes place in the absence of karyogamy between naturally occurring, homozygous a and alpha strains. This study provides the first description of the cell biology of the mating process of C. albicans.

| S-EPMC141171 | biostudies-literature

The 'obligate diploid' Candida albicans forms mating-competent haploids.

Project description:Candida albicans, the most prevalent human fungal pathogen, is considered to be an obligate diploid that carries recessive lethal mutations throughout the genome. Here we demonstrate that C. albicans has a viable haploid state that can be derived from diploid cells under in vitro and in vivo conditions, and that seems to arise through a concerted chromosome loss mechanism. Haploids undergo morphogenetic changes like those of diploids, including the yeast-hyphal transition, chlamydospore formation and a white-opaque switch that facilitates mating. Haploid opaque cells of opposite mating type mate efficiently to regenerate the diploid form, restoring heterozygosity and fitness. Homozygous diploids arise spontaneously by auto-diploidization, and both haploids and auto-diploids show a similar reduction in fitness, in vitro and in vivo, relative to heterozygous diploids, indicating that homozygous cell types are transient in mixed populations. Finally, we constructed stable haploid strains with multiple auxotrophies that will facilitate molecular and genetic analyses of this important pathogen.

| S-EPMC3583542 | biostudies-other

Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans.

Project description:Candida albicans is the most common fungal pathogen in humans, causing both debilitating mucosal infections and potentially life-threatening systemic infections. Until recently, C. albicans was thought to be strictly asexual, existing only as an obligate diploid. A cryptic mating cycle has since been uncovered in which diploid a and alpha cells undergo efficient cell and nuclear fusion, resulting in tetraploid a/alpha mating products. Whereas mating between a and alpha cells has been established (heterothallism), we report here two pathways for same-sex mating (homothallism) in C. albicans. First, unisexual populations of a cells were found to undergo autocrine pheromone signalling and same-sex mating in the absence of the Bar1 protease. In both C. albicans and Saccharomyces cerevisiae, Bar1 is produced by a cells and inactivates mating pheromone alpha, typically secreted by alpha cells. C. albicans Deltabar1 a cells were shown to secrete both a and alpha mating pheromones; alpha-pheromone activated self-mating in these cells in a process dependent on Ste2, the receptor for alpha-pheromone. In addition, pheromone production by alpha cells was found to promote same-sex mating between wild-type a cells. These results establish that homothallic mating can occur in C. albicans, revealing the potential for genetic exchange even within unisexual populations of the organism. Furthermore, Bar1 protease has an unexpected but pivotal role in determining whether sexual reproduction can potentially be homothallic or is exclusively heterothallic. These findings also have implications for the mode of sexual reproduction in related species that propagate unisexually, and indicate a role for specialized sexual cycles in the survival and adaptation of pathogenic fungi.

| S-EPMC2866515 | biostudies-literature

pH Regulates White-Opaque Switching and Sexual Mating in Candida albicans.

Project description:As a successful commensal and pathogen of humans, Candida albicans encounters a wide range of environmental conditions. Among them, ambient pH, which changes frequently and affects many biological processes in this species, is an important factor, and the ability to adapt to pH changes is tightly linked with pathogenesis and morphogenesis. In this study, we report that pH has a profound effect on white-opaque switching and sexual mating in C. albicans. Acidic pH promotes white-to-opaque switching under certain culture conditions but represses sexual mating. The Rim101-mediated pH-sensing pathway is involved in the control of pH-regulated white-opaque switching and the mating response. Phr2 and Rim101 could play a major role in acidic pH-induced opaque cell formation. Despite the fact that the cyclic AMP (cAMP) signaling pathway does not play a major role in pH-regulated white-opaque switching and mating, white and opaque cells of the cyr1/cyr1 mutant, which is defective in the production of cAMP, showed distinct growth defects under acidic and alkaline conditions. We further discovered that acidic pH conditions repressed sexual mating due to the failure of activation of the Ste2-mediated α-pheromone response pathway in opaque A: cells. The effects of pH changes on phenotypic switching and sexual mating could involve a balance of host adaptation and sexual reproduction in C. albicans.

| S-EPMC4621312 | biostudies-literature

Genetic regulation of the development of mating projections in Candida albicans.

Project description:Candida albicans is a major human fungal pathogen, capable of switching among a range of morphological types, such as the yeast form, including white and opaque cell types and the GUT (gastrointestinally induced transition) cell type, the filamentous form, including hyphal and pseudohyphal cell types, and chlamydospores. This ability is associated with its commensal and pathogenic life styles. In response to pheromone, C. albicans cells are able to form long mating projections resembling filaments. This filamentous morphology is required for efficient sexual mating. In the current study, we report the genetic regulatory mechanisms controlling the development of mating projections in C. albicans. Ectopic expression of MTLα1 in "a" cells induces the secretion of α-pheromone and promotes the development of mating projections. Using this inducible system, we reveal that members of the pheromone-sensing pathway (including the pheromone receptor), the Ste11-Hst7-Cek1/2 mediated MAPK signalling cascade, and the RAM pathway are essential for the development of mating projections. However, the cAMP/PKA signalling pathway and a number of key regulators of filamentous growth such as Hgc1, Efg1, Flo8, Tec1, Ume6, and Rfg1 are not required for mating projection formation. Therefore, despite the phenotypic similarities between filaments and mating projections in C. albicans, distinct mechanisms are involved in the regulation of these two morphologies.

| S-EPMC7048184 | biostudies-literature

Tca1, the retrotransposon-like element of Candida albicans, is a degenerate and inactive element.

Project description:Candida albicans is an asexual fungus and as such must rely on mechanisms other than sexual recombination to generate genetic diversity. Retrotransposons are ubiquitous genetic elements known to generate multiple types of genomic alterations. We have further investigated the nature of the retrotransposon-like element Tca1 in C. albicans. Tca1 is present at two loci in strain SC5314. Both loci have now been cloned, and one element was sequenced in its entirety. This element was flanked by alpha elements, or long terminal repeats (LTRs), and contained an intervening region of 5,614 bp. The intervening region was highly degenerate and contained no extended open reading frames, indicating that Tca1 is not a functional element. Partial sequence determination demonstrated that the elements from the two loci were nearly identical. Genetic manipulation of the elements showed that both loci were heterozygous for Tca1, that both were transcriptionally active, and that deletion of both had no effect on growth rate or germ tube formation. Thus, it is unclear why this nonfunctional, highly degenerate element has been maintained in many clinical isolates.

| S-EPMC107336 | biostudies-literature

Genetic control of Candida albicans biofilm development.

Project description:Candida species cause frequent infections owing to their ability to form biofilms - surface-associated microbial communities - primarily on implanted medical devices. Increasingly, mechanistic studies have identified the gene products that participate directly in the development of Candida albicans biofilms, as well as the regulatory circuitry and networks that control their expression and activity. These studies have uncovered new mechanisms and signals that govern C. albicans biofilm development and associated drug resistance, thus providing biological insight and therapeutic foresight.

| S-EPMC3891587 | biostudies-literature

A temperature-regulated, retrotransposon-like element from Candida albicans.

Project description:A repetitive element was isolated from the genome of Candida albicans. This repetitive element, which we designated alpha, was localized to a 500-bp fragment of genomic DNA. The alpha element was dispersed in the genome and varied in copy number and genomic location in the strains examined. Analyses of various loci containing the alpha element identified a locus containing a composite element. This composite element consisted of two direct repeats of the alpha element separated by approximately 5.5 kb of DNA, a structural arrangement similar to that of retrovirus-like transposable elements. The flanking alpha elements of the composite structure were 388 bp in length and were identical in sequence. They were bounded by the nucleotides 5'-TG. ... CA-3', which were part of a delimiting inverted repeat, a feature conserved in the long terminal repeats of retroviruses and retrovirus-like elements. As in retrovirus-like elements, the entire composite element, including the alpha elements, was transcribed into an approximately unit-length mRNA. The expression of this transcript was greatly increased when cells were grown at 25 versus 37 degrees C. As has been found in many retrotransposons, the composite element was flanked by a 5-bp duplication and varied in both copy number and genomic location in various strains. We conclude that the composite element is a retrotransposon-like element, and we have designated this element Tca1. We suggest that Tca1 may be relevant to the genomic evolution of C. albicans and the pathogenic potential of the organism.

| S-EPMC206508 | biostudies-other

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