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Eukaryotic Cell, October 2003, p. 1025-1035, Vol. 2, No. 5
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.5.1025-1035.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Phospholipid-Binding Protein Cts1 Controls Septation and Functions Coordinately with Calcineurin in Cryptococcus neoformans

Deborah S. Fox,1,2 Gary M. Cox,1,2 and Joseph Heitman1,2,3,4*

Departments of Molecular Genetics and Microbiology,1 Pharmacology and Cancer Biology,3 Medicine,2 Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina4

Received 16 June 2003/ Accepted 6 August 2003

Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients. The Ca2+-calmodulin-activated protein phosphatase calcineurin is necessary for virulence of C. neoformans. Mutants lacking the calcineurin catalytic (Cna1) or regulatory (Cnb1) subunit fail to grow at elevated temperature and are defective in virulence and hyphal elongation. Here we isolated a multicopy suppressor gene, CTS1, which restores growth of a calcineurin mutant strain at 37°C. The CTS1 gene (for calcineurin temperature suppressor 1) encodes a protein containing a C2 domain and a leucine zipper motif that may function as an effector of calcineurin. The CTS1 gene was disrupted by homologous recombination, and cts1 mutants were viable but exhibited defects in cell separation, growth, mating, and haploid fruiting. In addition, cts1 mutants were inviable when calcineurin was mutated or inhibited. Taken together, these findings suggest that calcineurin and Cts1 function in parallel pathways that regulate growth, cell separation, and hyphal elongation.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, 322 CARL Bldg., Box 3546, Duke University Medical Center, Research Drive, Durham, NC 27710. Phone: (919) 684-2824. Fax: (919) 684-5458. E-mail: heitm001{at}duke.edu.

Eukaryotic Cell, October 2003, p. 1025-1035, Vol. 2, No. 5
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.5.1025-1035.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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