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MBC in Press, published online ahead of print March 5, 2008
Mol. Biol. Cell 10.1091/mbc.E07-09-0960

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Submitted on September 24, 2007
Revised on February 20, 2008
Accepted on February 27, 2008

The Yak1 Kinase is Involved in the Initiation and Maintenance of Hyphal Growth in Candida albicans

Sophie Goyard,* Philipp Knechtle,*{dagger} Murielle Chauvel,* Adeline Mallet,{ddagger} Marie-Christine Prévost,{ddagger} Caroline Proux,{sect} Jean-Yves Coppée,{sect} Patrick Schwartz,|| Françoise Dromer,|| Hyunsook Park,¶ Scott G. Filler,¶ Guilhem Janbon,|| and Christophe d’Enfert*

*Unité Biologie et Pathogénicité Fongiques, INRA USC2019, {ddagger}Plate-forme de Microscopie Ultrastructurale, {sect}Plate-Forme 2 – Puces à ADN, Pasteur Génopole Ile-de-France, and ||Unité de Mycologie Moléculaire, CNRS URA3012, Institut Pasteur, Paris, France; Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1737

Monitoring Editor: Daniel Lew

Members of the dual-specificity tyrosine-phosphorylated and regulated kinases (DYRK) family perform a variety of functions in eukaryotes. We used gene disruption, targeted pharmacologic inhibition, and genome-wide transcriptional profiling to dissect the function of the Yak1 DYRK in the human fungal pathogen, Candida albicans. C. albicans strains with mutant yak1 alleles showed defects in the yeast-to-hypha transition and in maintaining hyphal growth. They also could not form biofilms. Despite their in vitro filamentation defect, C. albicans yak1{Delta}/yak1{Delta} mutants remained virulent in animal models of systemic and oropharyngeal candidiasis. Transcriptional profiling showed that Yak1 was necessary for the up-regulation of only a subset of hypha-induced genes. Although downstream targets of the Tec1 and Bcr1 transcription factors were down-regulated in the yak1{Delta}/yak1{Delta} mutant, TEC1 and BCR1 were not. Furthermore, 63% of Yak1-dependent, hypha specific genes have been reported to be negatively regulated by the transcriptional repressor, Tup1, and inactivation of TUP1 in the yak1{Delta}/yak1{Delta} mutant restored filamentation, suggesting that Yak1 may function upstream of Tup1 in governing hyphal emergence and maintenance.

{dagger}Present address: Evolva SA, Hagmattstrasse 6, 4123 Allschwil, Switzerland.

Address correspondence to: Christophe d’Enfert (denfert{at}pasteur.fr)




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