Motor Protein Myo5p Is Required To Maintain the Regulatory Circuit Controlling
            <i>WOR1</i>
            Expression in Candida albicans

Kachurina, Nadezda; Turcotte, Bernard; Whiteway, Malcolm

doi:10.1128/ec.00021-12

Cited by 3 publications

(3 citation statements)

References 54 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Opaque cells were never observed in the med3⌬/⌬ or med15⌬/⌬ strain, even under conditions of CO 2 induction (see below), using either colony or single-cell morphology as a criterion. Previously, the inability to switch from the white state to the opaque state was observed only in the wor1⌬/⌬ mutant (38)(39)(40), wor2⌬/⌬ mutant (41), myo5⌬/⌬ mutant (60), and sla2⌬/⌬ mutant (60). In these mutants, the master regulation circuit was broken either by the absence of essential players or by the disruption of the cytoskeleton.…”

Section: Resultsmentioning

confidence: 99%

Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

2013

View full text Add to dashboard Cite

The multisubunit eukaryotic Mediator complex integrates diverse positive and negative gene regulatory signals and transmits them to the core transcription machinery. Mutations in individual subunits within the complex can lead to decreased or increased transcription of certain subsets of genes, which are highly specific to the mutated subunit. Recent studies suggest a role for Mediator in epigenetic silencing. Using white-opaque morphological switching in Candida albicans as a model, we have shown that Mediator is required for the stability of both the epigenetic silenced (white) and active (opaque) states of the bistable transcription circuit driven by the master regulator Wor1. Individual deletions of eight C. albicans Mediator subunits have shown that different Mediator subunits have dramatically diverse effects on the directionality, frequency, and environmental induction of epigenetic switching. Among the Mediator deletion mutants analyzed, only Med12 has a steady-state transcriptional effect on the components of the Wor1 circuit that clearly corresponds to its effect on switching. The MED16 and MED9 genes have been found to be among a small subset of genes that are required for the stability of both the white and opaque states. Deletion of the Med3 subunit completely destabilizes the opaque state, even though the Wor1 transcription circuit is intact and can be driven by ectopic expression of Wor1. The highly impaired ability of the med3 deletion mutant to mate, even when Wor1 expression is ectopically induced, reveals that the activation of the Wor1 circuit can be decoupled from the opaque state and one of its primary biological consequences.

show abstract

Section: Resultsmentioning

confidence: 99%

Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

2013

View full text Add to dashboard Cite

show abstract

“…The WOR1 gene was discovered to be a "master regulator" of W-O switching; however, a role for WOR1 in pathogenesis has not been reported. Other genes involved in regulating the W-O switch include WOR2, CZF1, and MYO5, among others (27,28). Thus, both positive and negative phenotypic switching regulatory terms were needed to describe the regulators of phenotypic switching.…”

Section: Resultsmentioning

confidence: 99%

Improved Gene Ontology Annotation for Biofilm Formation, Filamentous Growth, and Phenotypic Switching in Candida albicans

et al. 2013

View full text Add to dashboard Cite

The opportunistic fungal pathogen Candida albicans is a significant medical threat, especially for immunocompromised patients. Experimental research has focused on specific areas of C. albicans biology, with the goal of understanding the multiple factors that contribute to its pathogenic potential. Some of these factors include cell adhesion, invasive or filamentous growth, and the formation of drug-resistant biofilms. The Gene Ontology (GO) (www.geneontology.org) is a standardized vocabulary that the Candida Genome Database (CGD) (www.candidagenome.org) and other groups use to describe the functions of gene products. To improve the breadth and accuracy of pathogenicity-related gene product descriptions and to facilitate the description of as yet uncharacterized but potentially pathogenicity-related genes in Candida species, CGD undertook a three-part project: first, the addition of terms to the biological process branch of the GO to improve the description of fungus-related processes; second, manual recuration of gene product annotations in CGD to use the improved GO vocabulary; and third, computational ortholog-based transfer of GO annotations from experimentally characterized gene products, using these new terms, to uncharacterized orthologs in other Candida species. Through genome annotation and analysis, we identified candidate pathogenicity genes in seven non-C. albicans Candida species and in one additional C. albicans strain, WO-1. We also defined a set of C. albicans genes at the intersection of biofilm formation, filamentous growth, pathogenesis, and phenotypic switching of this opportunistic fungal pathogen, which provides a compelling list of candidates for further experimentation.

show abstract

“…Deletion of either MYO3 or MYO5 is tolerated by cells, but a deletion of both genes causes defects in endocytosis as well as in growth (9,10). Myo5 of Candida albicans is also colocalized with actin patches at the bud and hyphal tips, and the myo5 mutant is impaired in polarized growth, hyphal formation, and endocytosis (11,12). Also, disruption of myo1 in Schizosaccharomyces pombe causes growth retardation and aberrance in cell morphology associated with an abnormal distribution of F-actin patches (13,14).…”

mentioning

confidence: 99%

A Novel Role of Fungal Type I Myosin in Regulating Membrane Properties and Its Association with d -Amino Acid Utilization in Cryptococcus gattii

Lamichhane

Garraffo²,

Cai³

et al. 2019

mBio

View full text Add to dashboard Cite

We found a novel role of Myo5, a type I myosin (myosin-I), and its fortuitous association with d-amino acid utilization in Cryptococcus gattii. Myo5 colocalized with actin cortical patches and was required for endocytosis. Interestingly, the myo5Δ mutant accumulated high levels of d-proline and d-alanine which caused toxicity in C. gattii cells. The myo5Δ mutant also accumulated a large set of substrates, such as membrane-permeant as well as non-membrane-permeant dyes, l-proline, l-alanine, and flucytosine intracellularly. Furthermore, the efflux rate of fluorescein was significantly increased in the myo5Δ mutant. Importantly, the endocytic defect of the myo5Δ mutant did not affect the localization of the proline permease and flucytosine transporter. These data indicate that the substrate accumulation phenotype is not solely due to a defect in endocytosis, but the membrane properties may have been altered in the myo5Δ mutant. Consistent with this, the sterol staining pattern of the myo5Δ mutant was different from that of the wild type, and the mutant was hypersensitive to amphotericin B. It appears that the changes in sterol distribution may have caused altered membrane permeability in the myo5Δ mutant, allowing increased accumulation of substrate. Moreover, myosin-I mutants generated in several other yeast species displayed a similar substrate accumulation phenotype. Thus, fungal type I myosin appears to play an important role in regulating membrane permeability. Although the substrate accumulation phenotype was detected in strains with mutations in the genes involved in actin nucleation, the phenotype was not shared in all endocytic mutants, indicating a complicated relationship between substrate accumulation and endocytosis. IMPORTANCE Cryptococcus gattii, one of the etiological agents of cryptococcosis, can be distinguished from its sister species Cryptococcus neoformans by growth on d-amino acids. C. gattii MYO5 affected the growth of C. gattii on d-amino acids. The myo5Δ cells accumulated high levels of various substrates from outside the cells, and excessively accumulated d-amino acids appeared to have caused toxicity in the myo5Δ cells. We provide evidence on the alteration of membrane properties in the myo5Δ mutants. Additionally, alteration in the myo5Δ membrane permeability causing higher substrate accumulation is associated with the changes in the sterol distribution. Furthermore, myosin-I in three other yeasts also manifested a similar role in substrate accumulation. Thus, while fungal myosin-I may function as a classical myosin-I, it has hitherto unknown additional roles in regulating membrane permeability. Since deletion of fungal myosin-I causes significantly elevated susceptibility to multiple antifungal drugs, it could serve as an effective target for augmentation of fungal therapy.

show abstract

Motor Protein Myo5p Is Required To Maintain the Regulatory Circuit Controlling WOR1 Expression in Candida albicans

Cited by 3 publications

References 54 publications

Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

Improved Gene Ontology Annotation for Biofilm Formation, Filamentous Growth, and Phenotypic Switching in Candida albicans

A Novel Role of Fungal Type I Myosin in Regulating Membrane Properties and Its Association with d -Amino Acid Utilization in Cryptococcus gattii

Contact Info

Product

Resources

About