The mitotic Cyclins Clb2p and Clb4p affect morphogenesis in Candida albicans
The mitotic Cyclins Clb2p and Clb4p affect morphogenesis in Candida albicans
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DOI：
10.1091/mbc.e04-12-1081
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发表时间：
2005-07-01
影响因子：
3.3
通讯作者：
Berman, J
中科院分区：
文献类型：
--
作者：
Bensen, ES;Clemente-Blanco, A;Berman, J
白色念珠菌改变细胞形态的能力对其引起感染的能力至关重要。由于细胞周期机制参与酿酒酵母的丝状生长，我们对两种白色念珠菌b型细胞周期蛋白CLB2和CLB4进行了详细的表征，以更好地了解白色念珠菌形态发生开关的分子机制。Clb2p和Clb4p水平均受细胞周期调控，在G2/M时达到峰值，在有丝分裂结束前下降。在菌丝诱导下，G1细胞周期蛋白Cln1p的积累被延长，而与酵母形式细胞相比，这两种Clb蛋白的积累被延迟，这表明CLB2和CLB4在两种形态下受到不同的调控，并且细胞周期蛋白出现的动态在酵母和菌丝形式的生长中有所不同。Clb2p缺失的细胞无法存活，并被含有两个细胞核的超细长突起所阻止，这表明Clb2p不是进入有丝分裂所必需的。与clb2p缺失的细胞不同，clb4p缺失的细胞是有活力的，并形成了组成性假菌丝。缺乏破坏盒结构域的Clb蛋白阻断了细胞周期进程，导致长突起的形成，这表明Clb2p和Clb4p在有丝分裂结束前必须被降解。此外，任何一种b型细胞周期蛋白的过表达都会降低丝状细胞生长的程度。综上所述，这些数据表明Clb2p和Clb4p通过负调控极化生长来调节白色念珠菌的形态发生。
The ability of Candida albicans to switch cellular morphologies is crucial for its ability to cause infection. Because the cell cycle machinery participates in Saccharomyces cerevisiae filamentous growth, we characterized in detail the two C. albicans B-type cyclins, CLB2 and CLB4, to better understand the molecular mechanisms that underlie the C. albicans morphogenic switch. Both Clb2p and Clb4p levels are cell cycle regulated, peaking at G2/M and declining before mitotic exit. On hyphal induction, the accumulation of the G1 cyclin Cln1p was prolonged, whereas the accumulation of both Clb proteins was delayed when compared with yeast form cells, indicating that CLB2 and CLB4 are differentially regulated in the two morphologies and that the dynamics of cyclin appearance differs between yeast and hyphal forms of growth. Clb2p-depleted cells were inviable and arrested with hyper-elongated projections containing two nuclei, suggesting that Clb2p is not required for entry into mitosis. Unlike Clb2p-depleted cells, Clb4p-depleted cells were viable and formed constitutive pseudohyphae. Clb proteins lacking destruction box domains blocked cell cycle progression resulting in the formation of long projections, indicating that both Clb2p and Clb4p must be degraded before mitotic exit. In addition, overexpression of either B-type cyclin reduced the extent of filamentous growth. Taken together, these data indicate that Clb2p and Clb4p regulate C. albicans morphogenesis by negatively regulating polarized growth.