The Yak1 kinase is involved in the initiation and maintenance of hyphal growth in Candida albicans.
Members of the dual-specificity tyrosine-phosphorylated and regulated kinase (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 yak1Delta/yak1Delta 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 yak1Delta/yak1Delta 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 yak1Delta/yak1Delta mutant restored filamentation, suggesting that Yak1 may function upstream of Tup1 in governing hyphal emergence and maintenance.
Goyard
Sophie
S
Unité Biologie et Pathogénicité Fongiques, Institut National de la Recherche Agronomique USC2019, Paris, France.
Knechtle
Philipp
P
Chauvel
Murielle
M
Mallet
Adeline
A
Prévost
Marie-Christine
MC
Proux
Caroline
C
Coppée
Jean-Yves
JY
Schwarz
Patrick
P
Schwartz
Patrick
P
Dromer
Françoise
F
Park
Hyunsook
H
Filler
Scott G
SG
Janbon
Guilhem
G
d'Enfert
Christophe
C
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal; D025301:Hyphae / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development* / Q000648:ultrastructure; D051379:Mice; D008969:Molecular Sequence Data; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014774:Virulence / Q000187:drug effects
C530021:4-amino-1-tert-butyl-3-(1'-naphthylmethyl)pyrazolo(3,4-d)pyrimidine; D005656:Fungal Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases