Calcineurin-Binding Protein Cbp1 Directs the Specificity of Calcineurin-Dependent Hyphal Elongation during Mating in Cryptococcus neoformans

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Published inEukaryotic Cell Vol. 4; no. 9; pp. 1526 - 1538
Main Authors Fox, Deborah S, Heitman, Joseph
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.09.2005
Subjects
Calcineurin - genetics
Calcineurin - metabolism
Cryptococcosis - metabolism
Cryptococcus neoformans - genetics
Cryptococcus neoformans - growth & development
Haploidy
Hyphae - growth & development
Mutagenesis, Site-Directed
Phosphorylation
Protein Binding
Virulence - genetics
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Abstract Classifications Services EC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue EC About EC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy EC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 1535-9778 Online ISSN: 1535-9786 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to EC .asm.org, visit: EC       
AbstractList Mating and virulence of the human fungal pathogen Cryptococcus neoformans are controlled by calcineurin, a serine-threonine-specific calcium-activated phosphatase that is the target of the immunosuppressive drugs cyclosporine A and FK506. In previous studies, a calcineurin binding protein (Cbp1, Rcn1, Dscr1/Csp1-3/MCIP1-3) that is conserved from yeasts to humans has been identified, but whether this protein functions to regulate calcineurin activity or facilitate calcineurin function as a signaling effector has been unclear. Here we show that, like calcineurin, Cbp1 is required for mating in C. neoformans . By contrast, Cbp1 plays no role in promoting calcineurin-dependent growth at 37°C and is not essential for haploid fruiting. Site-directed mutagenesis studies provide evidence that tandem phosphorylation and dephosphorylation of two serine residues in the conserved SP repeat motif are critical for Cbp1 function. Epistasis analysis supports models in which Cbp1 functions coordinately with calcineurin to direct hyphal elongation during mating. Taken together, these findings provide insights into the roles of Cbp1 as an accessory subunit or effector of calcineurin-specific signaling pathways, which may be features conserved among the calcipressins to govern calcineurin signaling in immune cells, cardiomyocytes, and neurons of multicellular eukaryotes.
Classifications Services EC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue EC About EC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy EC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 1535-9778 Online ISSN: 1535-9786 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to EC .asm.org, visit: EC       
Mating and virulence of the human fungal pathogen Cryptococcus neoformans are controlled by calcineurin, a serine-threonine-specific calcium-activated phosphatase that is the target of the immunosuppressive drugs cyclosporine A and FK506. In previous studies, a calcineurin binding protein (Cbp1, Rcn1, Dscr1/Csp1-3/MCIP1-3) that is conserved from yeasts to humans has been identified, but whether this protein functions to regulate calcineurin activity or facilitate calcineurin function as a signaling effector has been unclear. Here we show that, like calcineurin, Cbp1 is required for mating in C. neoformans. By contrast, Cbp1 plays no role in promoting calcineurin-dependent growth at 37 degrees C and is not essential for haploid fruiting. Site-directed mutagenesis studies provide evidence that tandem phosphorylation and dephosphorylation of two serine residues in the conserved SP repeat motif are critical for Cbp1 function. Epistasis analysis supports models in which Cbp1 functions coordinately with calcineurin to direct hyphal elongation during mating. Taken together, these findings provide insights into the roles of Cbp1 as an accessory subunit or effector of calcineurin-specific signaling pathways, which may be features conserved among the calcipressins to govern calcineurin signaling in immune cells, cardiomyocytes, and neurons of multicellular eukaryotes.
Author Joseph Heitman
Deborah S. Fox
AuthorAffiliation Research Institute for Children and Department of Pediatrics, Louisiana State Health Science Center, Children's Hospital, New Orleans, Louisiana 70118, 1 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710 2
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Notes Corresponding author. Mailing address for D. Fox: Research Institute for Children and Department of Pediatrics, Louisiana State Health Science Center, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA 70118. Phone: 504-986-2766. Fax: 504-986-2766. E-mail: dfox@chnola-research.org. Mailing address for J. Heitman: Department of Molecular Genetics and Microbiology, Duke University Medical Center, 322 CARL Building, Research Drive, Box 3546, Durham, NC 27710. E-mail: heitm001@duke.edu.
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Mating and virulence of the human fungal pathogen Cryptococcus neoformans are controlled by calcineurin, a serine-threonine-specific calcium-activated...
Mating and virulence of the human fungal pathogen Cryptococcus neoformans are controlled by calcineurin, a serine-threonine-specific calcium-activated...
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StartPage 1526
SubjectTerms Calcineurin - genetics
Calcineurin - metabolism
Cryptococcosis - metabolism
Cryptococcus neoformans - genetics
Cryptococcus neoformans - growth & development
Haploidy
Hyphae - growth & development
Mutagenesis, Site-Directed
Phosphorylation
Protein Binding
Virulence - genetics
Title Calcineurin-Binding Protein Cbp1 Directs the Specificity of Calcineurin-Dependent Hyphal Elongation during Mating in Cryptococcus neoformans
URI http://ec.asm.org/content/4/9/1526.abstract
https://www.ncbi.nlm.nih.gov/pubmed/16151246
https://pubmed.ncbi.nlm.nih.gov/PMC1214203
Volume 4
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