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PMID:20457806

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Citation

Zacchi, LF, Gomez-Raja, J and Davis, DA (2010) Mds3 regulates morphogenesis in Candida albicans through the TOR pathway. Mol. Cell. Biol. 30:3695-710

Abstract

The success of Candida albicans as a major human fungal pathogen is dependent on its ability to colonize and survive as a commensal on diverse mucosal surfaces. One trait required for survival and virulence in the host is the morphogenetic yeast-to-hypha transition. Mds3 was identified as a regulator of pH-dependent morphogenesis that functions in parallel with the classic Rim101 pH-sensing pathway. Microarray analyses revealed that mds3 Delta/Delta cells had an expression profile indicative of a hyperactive TOR pathway, including the preferential expression of genes encoding ribosomal proteins and a decreased expression of genes involved in nitrogen source utilization. The transcriptional and morphological defects of the mds3 Delta/Delta mutant were rescued by rapamycin, an inhibitor of TOR, and this rescue was lost in strains carrying the rapamycin-resistant TOR1-1 allele or an rbp1 Delta/Delta deletion. Rapamycin also rescued the transcriptional and morphological defects associated with the loss of Sit4, a TOR pathway effector, but not the loss of Rim101 or Ras1. The sit4 Delta/Delta and mds3 Delta/Delta mutants had additional phenotypic similarities, suggesting that Sit4 and Mds3 function similarly in the TOR pathway. Finally, we found that Mds3 and Sit4 coimmunoprecipitate. Thus, Mds3 is a new member of the TOR pathway that contributes to morphogenesis in C. albicans as a regulator of this key morphogenetic pathway.

Links

PubMed PMC2897559 Online version:10.1128/MCB.01540-09

Keywords

Base Sequence; Candida albicans/genetics; Candida albicans/growth & development; Candida albicans/metabolism; Candida albicans/pathogenicity; DNA Primers/genetics; DNA, Fungal/genetics; Fungal Proteins/genetics; Fungal Proteins/metabolism; Gene Expression Regulation, Developmental/drug effects; Gene Expression Regulation, Fungal/drug effects; Genes, Fungal; Humans; Morphogenesis/drug effects; Morphogenesis/genetics; Morphogenesis/physiology; Mutation; Oligonucleotide Array Sequence Analysis; Signal Transduction/drug effects; Sirolimus/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CANAX:RAS1

acts_upstream_of_or_within

GO:0036171: filamentous growth of a population of unicellular organisms in response to chemical stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAX:RAS1

acts_upstream_of_or_within

GO:1900439: positive regulation of filamentous growth of a population of unicellular organisms in response to chemical stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:MDS3

involved_in

GO:0031929: TOR signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:SIT4

acts_upstream_of_or_within

GO:0030447: filamentous growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:SIT4

acts_upstream_of_or_within

GO:0036244: cellular response to neutral pH

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:SIT4

acts_upstream_of_or_within

GO:0036171: filamentous growth of a population of unicellular organisms in response to chemical stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:SIT4

acts_upstream_of_or_within

GO:0036168: filamentous growth of a population of unicellular organisms in response to heat

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:SIT4

acts_upstream_of_or_within

GO:1900439: positive regulation of filamentous growth of a population of unicellular organisms in response to chemical stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:PACC

acts_upstream_of_or_within

GO:0036171: filamentous growth of a population of unicellular organisms in response to chemical stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:PACC

acts_upstream_of_or_within

GO:1900439: positive regulation of filamentous growth of a population of unicellular organisms in response to chemical stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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