Identification and Characterization of
 MFA1
 , the Gene Encoding
 Candida albicans
 a
 -Factor Pheromone

Dignard, Daniel; El-Naggar, A. L.; Logue, Mary E.; Butler, Geraldine; Whiteway, Malcolm

doi:10.1128/ec.00387-06

Cited by 40 publications

(59 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of these genes is selectively up-regulated in a cells by ␣-pheromone (Roberts et al, 2000). C. albicans has only one a-pheromone gene, MFA1, which is also selectively up-regulated in opaque a/a cells by ␣-pheromone (Dignard et al, 2007). Up-regulation of this gene exhibited the same dependencies on components of the opaque pheromone response pathway as shmooing and mating.…”

Section: Molecular Biology Of the Cell 966mentioning

confidence: 70%

The Same Receptor, G Protein, and Mitogen-activated Protein Kinase Pathway Activate Different Downstream Regulators in the Alternative White and Opaque Pheromone Responses ofCandida albicans

Song

Sahni

Daniels

et al. 2008

MBoC

251

View full text Add to dashboard Cite

Candida albicans must undergo a switch from white to opaque to mate. Opaque cells then release mating type-specific pheromones that induce mating responses in opaque cells. Uniquely in C. albicans, the same pheromones induce mating-incompetent white cells to become cohesive, form an adhesive basal layer of cells on a surface, and then generate a thicker biofilm that, in vitro, facilitates mating between minority opaque cells. Through mutant analysis, it is demonstrated that the pathways regulating the white and opaque cell responses to the same pheromone share the same upstream components, including receptors, heterotrimeric G protein, and mitogen-activated protein kinase cascade, but they use different downstream transcription factors that regulate the expression of genes specific to the alternative responses. This configuration, although common in higher, multicellular systems, is not common in fungi, and it has not been reported in Saccharomyces cerevisiae. The implications in the evolution of multicellularity in higher eukaryotes are discussed. INTRODUCTIONBoth single cell organisms and the individual cells of multicellular organisms must respond to a variety of environmental signals (Dorsky et al., 2000;Balázsi and Oltvai, 2005). In addition, in higher eukaryotes different cell types frequently respond to the same signal in unique ways (Rincón and Pedraza-Alva, 2003;Bacci et al., 2005;Dailey et al., 2005). In most cases, different signals interact with unique surface receptors that activate different signal transduction pathways, as has been demonstrated in Saccharomyces cerevisiae (Leberer et al., 1997;Gustin et al., 1998;Madhani and Fink, 1998;Elion, 2000). The mitogen-activated protein (MAP) kinase pathways have evolved as highly efficient, multipurpose signal transduction systems. S. cerevisiae uses multiple MAP kinase pathways, each one for a distinct signaling system, including the mating process, the filamentation process, cell wall integrity, ascospore formation, and osmoregulation (Levin and Errede, 1995;Gustin et al., 1998;Saito and Tatebayashi, 2004;Chen and Thorner, 2007). Several of these pathways share a limited number of components, but all are presumed to use different receptors to elicit very different responses. In the mating process of S. cerevisiae, a cells release a-factor that interacts with the a-receptor on ␣ cells, and ␣ cells release ␣-factor that interacts with the ␣-receptor on a cells. These alternative signals are then transduced through the same heterotrimeric G protein to activate the same MAP kinase pathway, which in turn activates the same downstream regulators that elicit similar mating responses, including G1 arrest, polarization, and shmooing (Sprague et al., 1983;Bender and Sprague, 1986;Leberer et al., 1997). Other fungi, including Magnaporthe grisea (Dixon et al., 1999;Zhao et al., 2005b) Neurospora crassa (Li et al., 2005), and Cryptococcus neoformans (Davidson et al., 2003;Kraus et al., 2003;Bahn et al., 2005) also use MAP kinase pathways for a variety of responses...

show abstract

Section: Molecular Biology Of the Cell 966mentioning

confidence: 70%

The Same Receptor, G Protein, and Mitogen-activated Protein Kinase Pathway Activate Different Downstream Regulators in the Alternative White and Opaque Pheromone Responses ofCandida albicans

Song

Sahni

Daniels

et al. 2008

MBoC

251

View full text Add to dashboard Cite

show abstract

“…In hemiascomycete yeast, STE2 encodes the receptor for α pheromone, whereas STE3 encodes the receptor for a pheromone (38). Loss of STE2 therefore prevents mating of a cells, whereas loss of STE3 prevents mating of α cells.…”

Section: Resultsmentioning

confidence: 99%

Discovery of a phenotypic switch regulating sexual mating in the opportunistic fungal pathogen Candida tropicalis

Porman

Alby

Hirakawa

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

111

151

View full text Add to dashboard Cite

Sexual reproduction can promote genetic diversity in eukaryotes, and yet many pathogenic fungi have been labeled as obligate asexual species. It is becoming increasingly clear, however, that cryptic sexual programs may exist in some species, and that efficient mating requires the necessary developmental switch to be triggered. In this study we investigate Candida tropicalis, an important human fungal pathogen that has been reported to be asexual. Significantly, we demonstrate that C. tropicalis uses a phenotypic switch to regulate a cryptic program of sexual mating. Thus, diploid a and α cells must undergo a developmental transition to the mating-competent form, and only then does efficient cell-cell conjugation take place resulting in the formation of stable a/α tetraploids. We show that both the phenotypic switch and sexual mating depend on the conserved transcriptional regulator Wor1, which is regulated by temperature in other fungal species. In contrast, C. tropicalis mating occurs efficiently at both 25°C and 37°C, suggesting that it could occur in the mammalian host and have direct consequences for the outcome of an infection. Transcriptional profiling further reveals that ≈400 genes are differentially expressed between the two phenotypic states, including the regulatory factor Wor1. Taken together, our results demonstrate that C. tropicalis has a unique sexual program, and that entry to this program is controlled via a Wor1-mediated, metastable switch. These observations have direct implications for the regulation and evolution of cryptic sexual programs in related fungal pathogens.epigenetic | recombination | bistability

show abstract

“…These classes differ based on their mode of spore generation, either inside (Ascomycetes) or outside (Basidiomycetes) of the mother cell. Recent studies indicate they also differ in the types of pheromone precursors they secrete, with Ascomycetes producing both hydrophobic and hydrophilic pheromones and Basidiomycetes producing solely hydrophobic ones such as afactor (32,38,41,51,79,269). This issue is discussed in detail below.…”

Section: Lipophilic Pheromones Are Common Among Fungimentioning

confidence: 99%

“…The Ascomycetes Secrete Both Hydrophobic (Prenylated) and Hydrophilic (Unmodified) Pheromones, Analogous to S. cerevisiae a-Factor and ␣-Factor Similar to the case for S. cerevisiae, most Ascomycetes examined to date encode both hydrophobic (a-factor-like) and hydrophilic (␣-factor-like) pheromones, expressed by two opposite mating types (41,79,138,269). In general, in cases where the DNA sequence is known, the precursors for the lipophilic pheromones are relatively short, ranging in length from ϳ23 to 45 amino acids (138).…”

Section: Lipophilic Pheromones Are Common Among Fungimentioning

confidence: 99%

Biogenesis of the Saccharomyces cerevisiae Pheromone a -Factor, from Yeast Mating to Human Disease

Michaelis¹,

Barrowman²

2012

Microbiol Mol Biol Rev

106

View full text Add to dashboard Cite

SUMMARY The mating pheromone a -factor secreted by Saccharomyces cerevisiae is a farnesylated and carboxylmethylated peptide and is unusually hydrophobic compared to other extracellular signaling molecules. Mature a -factor is derived from a precursor with a C-terminal CAAX motif that directs a series of posttranslational reactions, including prenylation, endoproteolysis, and carboxylmethylation. Historically, a -factor has served as a valuable model for the discovery and functional analysis of CAAX-processing enzymes. In this review, we discuss the three modules comprising the a -factor biogenesis pathway: (i) the C-terminal CAAX-processing steps carried out by Ram1/Ram2, Ste24 or Rce1, and Ste14; (ii) two sequential N-terminal cleavage steps, mediated by Ste24 and Axl1; and (iii) export by a nonclassical mechanism, mediated by the ATP binding cassette (ABC) transporter Ste6. The small size and hydrophobicity of a -factor present both challenges and advantages for biochemical analysis, as discussed here. The enzymes involved in a -factor biogenesis are conserved from yeasts to mammals. Notably, studies of the zinc metalloprotease Ste24 in S. cerevisiae led to the discovery of its mammalian homolog ZMPSTE24, which cleaves the prenylated C-terminal tail of the nuclear scaffold protein lamin A. Mutations that alter ZMPSTE24 processing of lamin A in humans cause the premature-aging disease progeria and related progeroid disorders. Intriguingly, recent evidence suggests that the entire a -factor pathway, including all three biogenesis modules, may be used to produce a prenylated, secreted signaling molecule involved in germ cell migration in Drosophila . Thus, additional prenylated signaling molecules resembling a -factor, with as-yet-unknown roles in metazoan biology, may await discovery.

show abstract

Identification and Characterization of MFA1 , the Gene Encoding Candida albicans a -Factor Pheromone

Cited by 40 publications

References 49 publications

The Same Receptor, G Protein, and Mitogen-activated Protein Kinase Pathway Activate Different Downstream Regulators in the Alternative White and Opaque Pheromone Responses ofCandida albicans

The Same Receptor, G Protein, and Mitogen-activated Protein Kinase Pathway Activate Different Downstream Regulators in the Alternative White and Opaque Pheromone Responses ofCandida albicans

Discovery of a phenotypic switch regulating sexual mating in the opportunistic fungal pathogen Candida tropicalis

Biogenesis of the Saccharomyces cerevisiae Pheromone a -Factor, from Yeast Mating to Human Disease

Contact Info

Product

Resources

About