Candida albicans protein kinase CaHsl1p regulates cell elongation and virulence
Candida albicans protein kinase CaHsl1p regulates cell elongation and virulence
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DOI：
10.1111/j.1365-2958.2004.04405.x
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发表时间：
2004-11
影响因子：
3.6
通讯作者：
T. Umeyama;A. Kaneko;Y. Nagai;Nozomu Hanaoka;Koichi Tanabe;Y. Takano;M. Niimi;Y. Uehara
中科院分区：
文献类型：
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作者：
T. Umeyama;A. Kaneko;Y. Nagai;Nozomu Hanaoka;Koichi Tanabe;Y. Takano;M. Niimi;Y. Uehara
酿酒酵母 Hsl1p 是一种调节细胞形态的 Ser/Thr 蛋白激酶。我们鉴定了白色念珠菌 CaHSL1 并分析了其在白色念珠菌中的功能。缺乏CaHsl1p的细胞在酵母生长条件下表现出丝状生长，并且在菌丝生长条件下，丝状伸长速度比野生型细胞更快，表明它在抑制细胞伸长中发挥作用。绿色荧光蛋白标记的 CaHsl1p 与隔膜复合物在酵母生长期间共定位于芽颈，或在菌丝生长期间共定位于有效的分隔位点，正如酿酒酵母中的定位所预期的那样。然而，septin 复合物的定位在 ΔCahsl1 中没有改变，表明 CaHsl1p 不参与 septin 组织。 CaHsl1p 以细胞周期依赖性方式表达，除 G1 期外，在整个细胞周期中均被磷酸化。在 ΔCahsl1 细胞中，CaHsl1p 可能的靶点 CaSwe1p 的磷酸化减少，而 CaCdc28p 酪氨酸 18 的磷酸化增加。酪氨酸 18 突变的 CaCdc28p 的额外拷贝或 CaSWE1 的缺失抑制了 CaHSL1 缺失引起的细胞伸长表型。此外，ΔCahsl1 在小鼠全身念珠菌病模型中表现出毒力降低。因此，CaHsl1p-CaSwe1p-CaCdc28p 途径在酵母和菌丝形式的细胞伸长以及白色念珠菌的毒力中显得很重要。
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 ΔCahsl1, 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 ΔCahsl1 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, ΔCahsl1 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.