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EMBO J

Title:		Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans
Author(s):		Cruz MC; Fox DS; Heitman J;
Address:		"Department of Genetics, The Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA"
Journal Title:		EMBO J
Year:		2001
Volume:		20
Issue:		5
Page Number:		1020 - 1032
DOI:		10.1093/emboj/20.5.1020
ISSN/ISBN:		0261-4189 (Print) 1460-2075 (Electronic) 0261-4189 (Linking)
Abstract:		"Cryptococcus neoformans is a fungal pathogen that causes meningitis in immunocompromised patients. Its growth is sensitive to the immunosuppressants FK506 and cyclosporin, which inhibit the Ca2+- calmodulin-activated protein phosphatase calcineurin. Calcineurin is required for growth at 37 degrees C and virulence of C.neoformans. We found that calcineurin is also required for mating. FK506 blocks mating of C.neoformans via FKBP12-dependent inhibition of calcineurin, and mutants lacking calcineurin are bilaterally sterile. Calcineurin is not essential for the initial fusion event, but is required for hyphal elongation and survival of the heterokaryon produced by cell fusion. It is also required for hyphal elongation in diploid strains and during asexual haploid fruiting of MATalpha cells in response to nitrogen limitation. Because mating and haploid fruiting produce infectious basidiospores, our studies suggest a second link between calcineurin and virulence of C.neoformans. Calcine urin regulates filamentation and 37 degrees C growth via distinct pathways. Together with studies revealing that calcineurin mediates neurite extension and neutrophil migration in mammals, our findings indicate that calcineurin plays a conserved role in the control of cell morphology"
Keywords:		"Calcineurin/genetics/*metabolism Calcineurin Inhibitors Cryptococcus neoformans/*cytology/drug effects/genetics/*growth & development Cyclosporine/pharmacology *Diploidy Gene Expression Regulation, Fungal Genes, Reporter *Haploidy Mating Factor Mutation P;"
Notes:		"MedlineCruz, M C Fox, D S Heitman, J eng T32 AI007392/AI/NIAID NIH HHS/ R01 AI042159/AI/NIAID NIH HHS/ AI42159/AI/NIAID NIH HHS/ T32 AI07391-10/AI/NIAID NIH HHS/ AI41937-S1/AI/NIAID NIH HHS/ P01 AI44975/AI/NIAID NIH HHS/ A139115/PHS HHS/ P01 AI044975/AI/NIAID NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England 2001/03/07 EMBO J. 2001 Mar 1; 20(5):1020-32. doi: 10.1093/emboj/20.5.1020"