<i>Candida albicans RIM101</i>
            pH Response Pathway Is Required for Host-Pathogen Interactions

Davis, Dana A.; Edwards, John E.; Mitchell, Aaron P.; Ibrahim, Ashraf S.

doi:10.1128/iai.68.10.5953-5959.2000

Cited by 250 publications

(231 citation statements)

References 25 publications

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“…Thus we can now ascribe functional importance to the activating Rim101p cleavage that occurs even in acidic media in S. cerevisiae (32). In addition, these observations may explain why C. albicans rim101/ rim101 strains grow in the liver, but not in the kidney, in infected mice (8): replication in the kidney probably requires greater salt tolerance. Whether Rim101p/PacC pathways in other fungi have similar roles in ion homeostasis remains to be determined.…”

Section: Discussionmentioning

confidence: 94%

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Alkaline Response Genes of Saccharomyces cerevisiaeand Their Relationship to the RIM101 Pathway

Lamb¹,

Xu²,

Diamond³

et al. 2001

Journal of Biological Chemistry

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Environmental pH exerts broad control over growth and differentiation, but the molecular responses to external pH changes are poorly understood. Here we have used open reading frame macroarray hybridization to identify alkaline response genes in Saccharomyces cerevisiae. Northern or lacZ fusion assays confirmed the alkaline induction of two ion pump genes (ENA1 and VMA4), several ion limitation genes (CTR3, FRE1, PHO11/12, and PHO84), a siderophore-iron transporter gene (ARN4/ENB1), two transcription factor genes (NRG2 and TIS11), and two predicted membrane protein genes (YAR068W/YHR214W and YOL154W). Unlike ENA1 and SHC1, these new alkaline response genes are not induced by high salinity. The known pH-responsive genes in other fungi depend on the conserved PacC/ Rim101p transcription factor, but induction of several of these new genes relied upon Rim101p-independent pH signaling mechanisms. Rim101p-dependent genes were also dependent on Rim13p, a protease required for Rim101p processing. The Rim101p-dependent gene VMA4 is required for growth in alkaline conditions, illustrating how Rim101p may control adaptation. Because Rim101p activates ion pump genes, we tested the role of RIM101 in ion homeostasis and found that RIM101 promotes resistance to elevated cation concentrations. Thus, gene expression surveys can reveal new functions for characterized transcription factors in addition to uncovering physiological responses to environmental conditions.

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Section: Discussionmentioning

confidence: 94%

“…Extracellular pH is a key environmental signal that influences growth, physiology, and differentiation (1)(2)(3)(4)(5)(6)(7)(8)(9). Specialized responses to pH changes have been characterized in many organisms, but there is limited information concerning the extent and general features of such a response.…”

mentioning

confidence: 99%

Alkaline Response Genes of Saccharomyces cerevisiaeand Their Relationship to the RIM101 Pathway

Lamb¹,

Xu²,

Diamond³

et al. 2001

Journal of Biological Chemistry

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219

243

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“…In order to construct strain BWP17 ctr1DD/HIS1 : : CTR1 a 1888 bp fragment was amplified by PCR using genomic DNA from strain SC5314 (Gillum et al, 1984) as a template and primers CaCTR12854 and CaCTR1+1057 (Table 1). The resulting fragment was digested with SalI and introduced into the equivalent restriction site in pGEM-HIS1 (Davis et al, 2000;Wilson et al, 1999). The resulting construct (pGEM-HIS1/CTR1) contained the entire CaCTR1 ORF flanked by 844 bp of upstream and 288 bp of downstream sequences.…”

Section: Methodsmentioning

confidence: 99%

“…We subsequently tested these strains along with the wild-type control strain, DAY185 (Davis et al, 2000), for the mutant phenotypes associated with the lack of copper uptake (Fig. 6).…”

Section: Albicans Ctr1 Expression Responds To Copper Availabilitymentioning

confidence: 99%

The Candida albicans CTR1 gene encodes a functional copper transporter

2003

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Copper and iron uptake in Saccharomyces cerevisiae are linked through a high-affinity ferric/cupric-reductive uptake system. Evidence suggests that a similar system operates in Candida albicans. The authors have identified a C. albicans gene that is able to rescue a S. cerevisiae ctr1/ctr3-null mutant defective in high-affinity copper uptake. The 756 bp ORF, designated CaCTR1, encodes a 251 amino acid protein with a molecular mass of 27·8 kDa. Comparisons between the deduced amino acid sequence of the C. albicans Ctr1p and S. cerevisiae Ctr1p indicated that they share 39·6 % similarity and 33·0 % identity over their entire length. Within the predicted protein product of CaCTR1 there are putative transmembrane regions and sequences that resemble copper-binding motifs. The promoter region of CaCTR1 contains four sequences with significant identity to S. cerevisiae copper response elements. CaCTR1 is transcriptionally regulated in S. cerevisiae in response to copper availability by the copper-sensing transactivator Mac1p. Transcription of CaCTR1 in C. albicans is also regulated in a copper-responsive manner. This raises the possibility that CaCTR1 may be regulated in C. albicans by a Mac1p-like transactivator. A C. albicans ctr1-null mutant displays phenotypes consistent with the lack of copper uptake including growth defects in low-copper and low-iron conditions, a respiratory deficiency and sensitivity to oxidative stress. Furthermore, changes in morphology were observed in the C. albicans ctr1-null mutant. It is proposed that CaCTR1 facilitates transport of copper into the cell.

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“…The C. albicans strains are derivatives of BWP17 (51). The wildtype strains were DAY185 (URA3 + ARG4 + HIS1 + ) and DAY286 (URA3 + ARG4 + ) (52). The C. albicans sam37ΔΔ mutant and the sam37ΔΔ mutant overexpressing SAM35 (sam37ΔΔ SAM35↑↑) under the strong constitutive promoter TEF1 have been described previously (35).…”

Section: Methodsmentioning

confidence: 99%

A model system for mitochondrial biogenesis reveals evolutionary rewiring of protein import and membrane assembly pathways

Hewitt¹,

Heinz

Shingú-Vázquez³

et al. 2012

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

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The controlled biogenesis of mitochondria is a key cellular system coordinated with the cell division cycle, and major efforts in systems biology currently are directed toward understanding of the control points at which this coordination is achieved. Here we present insights into the function, evolution, and regulation of mitochondrial biogenesis through the study of the protein import machinery in the human fungal pathogen, Candida albicans. Features that distinguish C. albicans from baker's yeast (Saccharomyces cerevisiae) include the stringency of metabolic control at the level of oxygen consumption, the potential for ATP exchange through the porin in the outer membrane, and components and domains in the sorting and assembling machinery complex, a molecular machine that drives the assembly of proteins in the outer mitochondrial membrane. Analysis of targeting sequences and assays of mitochondrial protein import show that components of the electron transport chain are imported by distinct pathways in C. albicans and S. cerevisiae, representing an evolutionary rewiring of mitochondrial import pathways. We suggest that studies using this pathogen as a model system for mitochondrial biogenesis will greatly enhance our knowledge of how mitochondria are made and controlled through the course of the cell-division cycle.SAM complex | Omp85 | stop-transfer pathway | Sam51

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Candida albicans RIM101 pH Response Pathway Is Required for Host-Pathogen Interactions

Cited by 250 publications

References 25 publications

Alkaline Response Genes of Saccharomyces cerevisiaeand Their Relationship to the RIM101 Pathway

Alkaline Response Genes of Saccharomyces cerevisiaeand Their Relationship to the RIM101 Pathway

The Candida albicans CTR1 gene encodes a functional copper transporter

A model system for mitochondrial biogenesis reveals evolutionary rewiring of protein import and membrane assembly pathways

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