Document Detail


CDC42 is required for polarized growth in human pathogen Candida albicans.
MedLine Citation:
PMID:  12455975     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cdc42p is a member of the RAS superfamily of GTPases and plays an essential role in polarized growth in many eukaryotic cells. We cloned the Candida albicans CaCDC42 by functional complementation in Saccharomyces cerevisiae and analyzed its function in C. albicans. A double deletion of CaCDC42 was made in a C. albicans strain containing CaCDC42 under the control of the PCK1 promoter. When expression of the heterologous copy of CaCDC42 was repressed in this strain, the cells ceased proliferation. These arrested cells were large, round, and unbudded and contained predominantly two nuclei. The PCK1-mediated overexpression of wild-type CaCdc42p had no effect on cells. However, in cells overexpressing CaCdc42p containing the dominant-negative D118A substitution, proliferation was blocked and the arrested cells were large, round, unbudded, and multinucleated, similar to the phenotype of the cdc42 double-deletion strain. Cells overexpressing CaCdc42p containing the hyperactive G12V substitution also ceased proliferation in yeast growth medium; in this case the arrested cells were multinucleated and multibudded. An intact CAAX box is essential for the phenotypes associated with either CaCdc42p(G12V) or CaCdc42p(D118A) ectopic expression, suggesting that membrane attachment is involved in CaCdc42p function. In addition, the lethality caused by ectopic expression of CaCdc42p(G12V) was suppressed by deletion of CST20 but not by deletion of CaCLA4. CaCdc42p function was also examined under hypha-inducing conditions. Cdc42p depletion prior to hyphal induction trapped cells in a round, unbudded state, while depletion triggered at the same time as hyphal induction permitted the initiation of germ tubes that failed to be extended. Ectopic expression of either the G12V or D118A substitution protein modified hyphal formation in a CAAX box-dependent manner. Thus, CaCdc42p function appears important for polarized growth of both the yeast and hyphal forms of C. albicans.
Authors:
Sophia C Ushinsky; Doreen Harcus; Josee Ash; Daniel Dignard; Anne Marcil; Joachim Morchhauser; David Y Thomas; Malcolm Whiteway; Ekkehard Leberer
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Eukaryotic cell     Volume:  1     ISSN:  1535-9778     ISO Abbreviation:  Eukaryotic Cell     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-11-28     Completed Date:  2003-01-07     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  101130731     Medline TA:  Eukaryot Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  95-104     Citation Subset:  IM    
Affiliation:
Eukaryotic Genetics, National Research Council Biotechnology Research Institute, Montreal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Candida albicans / growth & development,  pathogenicity,  physiology*
DNA Primers
Gene Deletion
Gene Expression Regulation, Fungal
Genotype
Humans
Promoter Regions, Genetic
cdc42 GTP-Binding Protein / genetics*,  metabolism*
Chemical
Reg. No./Substance:
0/DNA Primers; EC 3.6.5.2/cdc42 GTP-Binding Protein
Comments/Corrections

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