Mutual co-regulation between GPI-N-acetylglucosaminyltransferase and ergosterol biosynthesis in <i>Candida albicans</i>

Victoria, Guiliana Soraya; Yadav, Bhawna; Hauhnar, Lalremruata; Jain, Priyanka; Bhatnagar, Shilpi; Komath, Sneha Sudha

doi:10.1042/bj20120143

Cited by 19 publications

(25 citation statements)

References 32 publications

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“…In their interaction with the ergosterol biosynthetic pathway too, the Cagpi14 mutants appear to be different from the Cagpi19 mutants. Unlike the latter, which showed azole sensitivity due to downregulation of ERG11 (Victoria et al ., ), the Cagpi14 mutants showed an upregulation of ERG11 . Such a response was also seen in Casmp3 mutant, which lacks the mannosyltransferase responsible for addition of the fourth mannose to the GPI anchor precursor (Victoria et al ., ).…”

Section: Resultsmentioning

confidence: 84%

“…Unlike the latter, which showed azole sensitivity due to downregulation of ERG11 (Victoria et al ., ), the Cagpi14 mutants showed an upregulation of ERG11 . Such a response was also seen in Casmp3 mutant, which lacks the mannosyltransferase responsible for addition of the fourth mannose to the GPI anchor precursor (Victoria et al ., ). Thus it would appear that upregulation of ERG11 is the common response of C .…”

Section: Resultsmentioning

confidence: 84%

“…It is particularly interesting to note the absence of interactions with the Ras pathway in Cagpi14 mutants, given that Cagpi19 and Cagpi2 mutants (each lacking an accessory subunit of the GPI‐GnT enzyme complex catalysing the first step of the pathway and defective in GPI biosynthesis) had altered hyphal morphogenesis specifically in response to altered Ras signalling (Victoria et al ., ; Yadav et al ., ). In other words, it would be reasonable to conclude that the interaction with Ras signalling that is observed in the mutants of the first step of GPI biosynthesis is specific to that step and not a result of a generic deficiency in GPI biosynthesis or a response to cell wall defects in these mutants.…”

Section: Resultsmentioning

confidence: 98%

“…Some GPI mutants have alterations in ergosterol biosynthesis and consequently exhibit altered response to drugs that target this pathway (Victoria et al ., ; Yadav et al ., ). In order to assess whether the ergosterol biosynthetic pathway was altered in the Cagpi14 mutants, the response of the mutants to azoles, the most common antifungals in current use, was examined.…”

Section: Resultsmentioning

confidence: 98%

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The catalytic subunit of the first mannosyltransferase in the GPI biosynthetic pathway affects growth, cell wall integrity and hyphal morphogenesis in Candida albicans

Singh

Chandra

Sah³

et al. 2016

Yeast

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CaGpi14 is the catalytic subunit of the first mannosyltransferase that is involved in the glycosylphosphatidylinositol (GPI) biosynthetic pathway in Candida albicans. We show that CaGPI14 is able to rescue a conditionally lethal gpi14 mutant of Saccharomyces cerevisiae, unlike its mammalian homologue. The depletion of this enzyme in C. albicans leads to severe growth defects, besides causing deficiencies in GPI anchor levels. In addition, CaGpi14 depletion results in cell wall defects and upregulation of the cell wall integrity response pathway. This in turn appears to trigger the osmoticstress dependent activation of the HOG1 pathway and an upregulation of HOG1 as well as its downstream target, SKO1, a known suppressor of expression of hyphae-specific genes. Consistent with this, mutants of CaGPI14 are unable to undergo hyphal transformations in different hyphae-inducing media, under conditions that produce abundant hyphae in the wild-type cells. Hyphal defects in the CaGPI14 mutants could not be attributed either to reduced protein kinase C activation or to defective Ras signalling in these cells but appeared to be driven by perturbations in the HOG1 pathway.

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Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 98%

See 2 more Smart Citations

The catalytic subunit of the first mannosyltransferase in the GPI biosynthetic pathway affects growth, cell wall integrity and hyphal morphogenesis in Candida albicans

Singh

Chandra

Sah³

et al. 2016

Yeast

View full text Add to dashboard Cite

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“…Cagpi2 cells are also more susceptible to killing by macrophages and recovery of live MH‐S cells is higher when incubated with Cagpi2 . CaGPI19 , on the other hand, exhibits a co‐regulation with ERG11, the lanosterol demethylase in the ergosterol biosynthetic pathway and the target of azole antifungals . Downregulation of CaGPI19 causes C. albicans to become sensitive to azole drugs due to a reduction in Erg11 levels.…”

Section: Biosynthesis Of the Gpi Anchormentioning

confidence: 99%

Generating anchors only to lose them: The unusual story of glycosylphosphatidylinositol anchor biosynthesis and remodeling in yeast and fungi

et al. 2018

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Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are present ubiquitously at the cell surface in all eukaryotes. They play a crucial role in the interaction of the cell with its external environment, allowing the cell to receive signals, respond to challenges, and mediate adhesion. In yeast and fungi, they also participate in the structural integrity of the cell wall and are often essential for survival. Roughly four decades after the discovery of the first GPI-APs, this review provides an overview of the insights gained from studies of the GPI biosynthetic pathway and the future challenges in the field. In particular, we focus on the biosynthetic pathway in Saccharomyces cerevisiae, which has for long been studied as a model organism. Where available, we also provide information about the GPI biosynthetic steps in other yeast/ fungi. Although the core structure of the GPI anchor is conserved across organisms, several variations are built into the biosynthetic pathway. The present Review specifically highlights these variations and their implications. There is growing evidence to suggest that several phenotypes are common to GPI deficiency and should be expected in GPI biosynthetic mutants. However, it appears that several phenotypes are unique to a specific step in the pathway and may even be species-specific. These could suggest the points at which the GPI biosynthetic pathway intersects with other important cellular pathways and could be points of regulation. They could be of particular significance in the study of pathogenic fungi and in identification of new and specific antifungal drugs/ drug targets. © 2018 IUBMB Life, 70(5):355-383, 2018.

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Saccharomyces cerevisiae Gpi2, an accessory subunit of the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis, selectively complements some of the functions of its homolog in Candida albicans

et al. 2014

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GPI2 encodes for one of the six accessory subunits of the GPI-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the first step of GPI biosynthesis in S. cerevisiae and C. albicans. It has been previously reported in S. cerevisiae that this subunit physically interacts with and negatively modulates Ras signaling. On the other hand, studies from our lab have shown that the homologous subunit in C. albicans is a positive modulator of Ras signaling. Are the functions of this subunit therefore strictly species dependent? We present here functional complementation studies on GPI2 from S. cerevisiae and C. albicans that were carried out to address this issue. Expression of CaGPI2 in a ScGPI2 conditional lethal mutant could not restore its growth defects. Likewise, ScGPI2 overexpression in a CaGPI2 heterozygous mutant could not restore its deficient GPI-GnT activity or reverse defects in its cell wall integrity and could only poorly restore filamentation. However, interestingly, ScGPI2 could restore lanosterol demethylase (CaERG11) levels and reverse azole resistance of the CaGPI2 heterozygote. It appeared to do this by regulating levels of another GPI-GnT subunit, CaGPI19, which we have previously shown to be involved in cross-talk with CaERG11. Thus, the effect of CaGPI2 on sterol biosynthesis in C. albicans is independent of its interaction with the GPI-GnT complex and Ras signaling pathways. In addition, the interaction of Gpi2 with other subunits of the GPI-GnT complex as well as with Ras signaling appears to have evolved differently in the two organisms.

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Mutual co-regulation between GPI-N-acetylglucosaminyltransferase and ergosterol biosynthesis in Candida albicans

Cited by 19 publications

References 32 publications

The catalytic subunit of the first mannosyltransferase in the GPI biosynthetic pathway affects growth, cell wall integrity and hyphal morphogenesis in Candida albicans

The catalytic subunit of the first mannosyltransferase in the GPI biosynthetic pathway affects growth, cell wall integrity and hyphal morphogenesis in Candida albicans

Generating anchors only to lose them: The unusual story of glycosylphosphatidylinositol anchor biosynthesis and remodeling in yeast and fungi

Saccharomyces cerevisiae Gpi2, an accessory subunit of the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis, selectively complements some of the functions of its homolog in Candida albicans

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