Woo Miyoung, Lee Kyunghee, Song Kiwon
Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, South Korea.
FEMS Microbiol Lett. 2003 Jan 21;218(1):195-202. doi: 10.1111/j.1574-6968.2003.tb11518.x.
The human fungal pathogen Candida albicans changes from a budding yeast form to a polarized hyphal form in response to various external conditions. Dimorphic switching of C. albicans has been implicated in the development of pathogenicity. Morphogenic transformation requires polarized cell growth and rearrangement of the cytoskeleton. We previously showed that myosins play key roles in the conversion from the bud to the hyphal form of C. albicans by inhibiting myosin activities with 2,3-butanedione-2-monoxime (BDM), a general myosin ATPase inhibitor. In this study we investigated the function of MYO2 in C. albicans using deletion mutants. The amino acid sequence of CaMYO2 shows 60% identity and 77% homology with MYO2 and 54% identity and 70% homology with MYO4 of budding yeast Saccharomyces cerevisiae, suggesting that CaMYO2 is the only class V myosin in C. albicans. Cells in which both CaMYO2 alleles were deleted were viable, suggesting that MYO2 is nonessential in C. albicans. The proliferation of CaMYO2delta cells, however, was sharply decreased. In addition, CaMYO2delta cells showed defects in assembly and polarized localization of F-actin as well as an inability to induce germ tube formation and hyphal growth. The deletion of CaMYO2 also disrupted the shape and migration of the nucleus. These results strongly suggest that CaMYO2 is essential for polarized growth and hyphal transition in C. albicans.
人类真菌病原体白色念珠菌会根据各种外部条件从出芽酵母形态转变为极性菌丝形态。白色念珠菌的二态性转换与致病性的发展有关。形态发生转变需要极性细胞生长和细胞骨架的重排。我们之前表明,肌球蛋白通过使用2,3 - 丁二酮 - 2 - 单肟(BDM,一种通用的肌球蛋白ATP酶抑制剂)抑制肌球蛋白活性,在白色念珠菌从芽形态向菌丝形态的转变中起关键作用。在本研究中,我们使用缺失突变体研究了白色念珠菌中MYO2的功能。白色念珠菌CaMYO2的氨基酸序列与酿酒酵母的MYO2显示出60%的同一性和77%的同源性,与MYO4显示出54%的同一性和70%的同源性,这表明CaMYO2是白色念珠菌中唯一的V类肌球蛋白。两个CaMYO2等位基因均被缺失的细胞是存活的,这表明MYO2在白色念珠菌中并非必需。然而,CaMYO2缺失细胞的增殖急剧下降。此外,CaMYO2缺失细胞在F - 肌动蛋白的组装和极性定位方面存在缺陷,并且无法诱导芽管形成和菌丝生长。CaMYO2的缺失还扰乱了细胞核的形状和迁移。这些结果强烈表明CaMYO2对于白色念珠菌的极性生长和菌丝转变至关重要。