Depletion of a polo-like kinase in Candida albicans activates cyclase-dependent hyphal-like growth
Depletion of a polo-like kinase in Candida albicans activates cyclase-dependent hyphal-like growth
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DOI：
10.1091/mbc.02-05-0076
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发表时间：
2003-05-01
影响因子：
3.3
通讯作者：
Whiteway, M
中科院分区：
文献类型：
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作者：
Bachewich, C;Thomas, DY;Whiteway, M
白色念珠菌的形态发生是一个重要的毒力决定因素，因为酵母和菌丝生长形式之间的二态转换可以增加发病机制。我们在白色念珠菌中发现了一种细胞周期调节的polo样激酶（PLK） CaCDC5，并证明关闭其表达会导致细胞周期缺陷和形态的剧烈变化。缺乏CaCdc5p的细胞在核分裂早期被阻断，纺锤体很短，染色质不分离。gfp标记的CaCdc5p定位于未分离的纺锤体极体、纺锤体和染色质上，这与酵母中同源Cdc5p在细胞周期早期的纺锤体伸长中所起的作用一致。引人注目的是，在酵母生长条件下，细胞周期缺陷伴随着菌丝样细丝的形成。24 h后，菌丝开始死亡，菌丝的生长是确定的。菌丝的形态、细胞质微管的组织、细胞核的定位以及菌丝特异性成分的表达与血清诱导的菌丝相似。纺丝形成需要CaCDC35，而不需要EFG1或CPH1，当酵母细胞暴露于羟基脲时，纺锤体伸长和相应的纺丝诱导也出现了类似的缺陷。由于CaCdc5p似乎不作为菌丝生长的直接抑制因子，数据表明CaCdc5p功能的靶标与菌丝样发育有关。因此，一个内部的，细胞周期相关的线索可以激活念珠菌的菌丝调节网络。
Morphogenesis in the fungal pathogen Candida albicans is an important virulence-determining factor, as a dimorphic switch between yeast and hyphal growth forms can increase pathogenesis. We identified CaCDC5, a cell cycle regulatory polo-like kinase (PLK) in C. albicans and demonstrate that shutting off its expression induced cell cycle defects and dramatic changes in morphology. Cells lacking CaCdc5p were blocked early in nuclear division with very short spindles and unseparated chromatin. GFP-tagged CaCdc5p localized to unseparated spindle pole bodies, the spindle, and chromatin, consistent with a role in spindle elongation at an earlier point in the cell cycle than that described for the homologue Cdc5p in yeast. Strikingly, the cell cycle defects were accompanied by the formation of hyphal-like filaments under yeast growth conditions. Filament growth was determinate, as the filaments started to die after 24 h. The filaments resembled serum-induced hyphae with respect to morphology, organization of cytoplasmic microtubules, localization of nuclei, and expression of hyphal-specific components. Filament formation required CaCDC35, but not EFG1 or CPH1 Similar defects in spindle elongation and a corresponding induction of filaments occurred when yeast cells were exposed to hydroxyurea. Because CaCdc5p does not appear to act as a direct repressor of hyphal growth, the data suggest that a target of CaCdc5p function is associated with hyphal-like development. Thus, an internal, cell cycle-related cue can activate hyphal regulatory networks in Candida.