Document Detail

RA domain-mediated interaction of Cdc35 with Ras1 is essential for increasing cellular cAMP level for Candida albicans hyphal development.
MedLine Citation:
PMID:  16856944     Owner:  NLM     Status:  MEDLINE    
Many Ras GTPases activate their effectors through binding at a conserved Ras association (RA) domain. An example is the activation of the budding yeast adenylate cyclase Cyr1 by Ras1 and Ras2. Candida albicans Ras1 is speculated to similarly activate Cdc35, the orthologue of Cyr1, for hyphal development. Here, we have investigated whether the RA domain mediates Ras1-Cdc35 interaction and how this interaction regulates cAMP levels and morphogenesis. Yeast two-hybrid assays suggested that Ras1 interacts only with the RA but not any other identifiable domains of Cdc35. The Ras1-RA interaction was further confirmed by in vitro binding assays of purified RA domain and Ras1 and by co-immunoprecipitation of Ras1 and Cdc35 from cell lysates. Substituting Ala for the conserved residue K(338) or L(349) in the RA domain or deleting the RA domain abolished the Ras1-RA or Ras1-Cdc35 interactions. cdc35 mutants with the RA domain deleted or carrying K388A or L349A mutation exhibited rather normal yeast growth but were completely defective in hyphal morphogenesis. Further, the mutants contained nearly wild-type levels of cAMP during yeast growth but were unable to increase it upon hyphal induction. These results suggest an essential role for the RA-mediated Ras1-Cdc35 interaction in raising cellular cAMP levels for hyphal morphogenesis.
Hao-Ming Fang; Yue Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular microbiology     Volume:  61     ISSN:  0950-382X     ISO Abbreviation:  Mol. Microbiol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-21     Completed Date:  2006-10-06     Revised Date:  2009-06-17    
Medline Journal Info:
Nlm Unique ID:  8712028     Medline TA:  Mol Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  484-96     Citation Subset:  IM    
Institute of Molecular and Cell Biology, ASTAR Biomedical Sciences Institutes, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore.
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MeSH Terms
Adenylate Cyclase / genetics,  metabolism*
Amino Acid Sequence
Candida albicans / physiology*
Conserved Sequence
Cyclic AMP / metabolism*
Fungal Proteins / genetics,  metabolism*
Hyphae / growth & development*,  metabolism
Membrane Proteins / genetics,  metabolism*
Molecular Sequence Data
Protein Interaction Mapping
Protein Structure, Tertiary
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
ras Proteins / genetics,  metabolism*
Reg. No./Substance:
0/Fungal Proteins; 0/Membrane Proteins; 0/Saccharomyces cerevisiae Proteins; 60-92-4/Cyclic AMP; EC protein, S cerevisiae; EC Proteins; EC Cyclase

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