Li Chang Run, Wang Yan Ming, De Zheng Xin, Liang Hui Yan, Tang Jason Chih Wei, Wang Yue
Molecular and Cell Biology Laboratory, Institute of Molecular and Cell Biology, Singapore.
J Cell Sci. 2005 Jun 15;118(Pt 12):2637-48. doi: 10.1242/jcs.02393. Epub 2005 May 24.
Formins are conserved eukaryotic proteins playing key roles in regulating cell polarity. We have characterized the roles of a formin CaBni1p in the polymorphic fungus Candida albicans. CaBni1p localized persistently to hyphal tips during hyphal growth but to distinct growth sites at different cell cycle stages during yeast growth. Cabni1Delta yeast cells exhibited several morphological defects, such as round and enlarged cells, widened bud necks and a random budding pattern. Although Cabni1Delta cells could still undergo yeast-hypha growth switch, the hyphae were markedly swollen. Cabni1Delta also showed defects in spindle and cytoplasmic microtubule orientation and positioning. Coincidentally, the spindle orientation protein CaKar9p in Cabni1Delta yeast cells appeared as multiple random cortical spots, in contrast to the single spot at the bud tip of many wild-type cells. Interestingly, several defects manifested in Cabni1Delta yeast cells were partially corrected during hyphal growth. We found that the second formin CaBnr1p was recruited to hyphal tips, while it localized only to the bud neck during yeast growth. This behavior of CaBnr1p may play a key role in correcting Cabni1Delta defects during hyphal growth. Cabni1Delta exhibited reduced virulence in mice. These results indicate that the formins play an important role in Candida albicans polarized growth and CaBni1p's function is required for virulence.
formin蛋白是保守的真核生物蛋白,在调节细胞极性中发挥关键作用。我们已经对多形真菌白色念珠菌中一种formin蛋白CaBni1p的作用进行了表征。CaBni1p在菌丝生长过程中持续定位于菌丝尖端,但在酵母生长过程中的不同细胞周期阶段定位于不同的生长位点。Cabni1Delta酵母细胞表现出几种形态缺陷,如细胞圆形且增大、芽颈变宽和出芽模式随机。尽管Cabni1Delta细胞仍可经历酵母-菌丝生长转换,但其菌丝明显肿胀。Cabni1Delta在纺锤体和细胞质微管的定向和定位方面也表现出缺陷。巧合的是,Cabni1Delta酵母细胞中的纺锤体定向蛋白CaKar9p呈现为多个随机的皮质斑点,这与许多野生型细胞芽尖处的单个斑点形成对比。有趣的是,Cabni1Delta酵母细胞中表现出的几种缺陷在菌丝生长过程中得到了部分纠正。我们发现第二种formin蛋白CaBnr1p被招募到菌丝尖端,而在酵母生长过程中它仅定位于芽颈。CaBnr1p的这种行为可能在纠正菌丝生长过程中的Cabni1Delta缺陷方面发挥关键作用。Cabni1Delta在小鼠中的毒力降低。这些结果表明formin蛋白在白色念珠菌的极性生长中起重要作用,并且CaBni1p的功能是毒力所必需的。