title: Candida albicans protein kinase CaHsl1p regulates cell elongation and virulence.
abstract: Saccharomyces cerevisiae Hsl1p is a Ser/Thr protein kinase that regulates cell morphology. We identified Candida albicans CaHSL1 and analysed its function in C. albicans. Cells lacking CaHsl1p exhibited filamentous growth under yeast growth conditions with the filaments elongating more quickly than did those of the wild type under hyphal growth conditions, suggesting that it plays a role in the suppression of cell elongation. Green fluorescent protein-tagged CaHsl1p colocalized with a septin complex to the bud neck during yeast growth or to a potent septation site during hyphal growth, as expected from the localization in S. cerevisiae. However, the localization of the septin complex did not change in DeltaCahsl1, suggesting that CaHsl1p does not participate in septin organization. CaHsl1p was expressed in a cell cycle-dependent manner and, except for the G1 phase, phosphorylated throughout the cell cycle. In DeltaCahsl1 cells, the phosphorylation of a possible CaHsl1p target CaSwe1p decreased, while that of CaCdc28p at tyrosine18 increased. Either an extra copy of the tyrosine18-mutated CaCdc28p or deletion of CaSWE1 suppressed the cell elongation phenotype caused by CaHSL1 deletion. Furthermore, DeltaCahsl1 exhibited reduced virulence in the mouse systemic candidiasis model. Thus, the CaHsl1p-CaSwe1p-CaCdc28p pathway appears important in the cell elongation of both the yeast and hyphal forms and to the virulence of C. albicans.
authors.affiliation: Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Umeyama
authors.forename: Aki
authors.initials: A
authors.lastname: Kaneko
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nagai
authors.forename: Nozomu
authors.initials: N
authors.lastname: Hanaoka
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanabe
authors.forename: Yukie
authors.initials: Y
authors.lastname: Takano
authors.forename: Masakazu
authors.initials: M
authors.lastname: Niimi
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Uehara
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000201:enzymology / Q000254:growth & development* / Q000472:pathogenicity* / Q000502:physiology; D002177:Candidiasis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009024:Morphogenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D017346:Protein Serine-Threonine Kinases