College of Life Sciences, Huaibei Normal University, Huaibei 235000, Anhui, China.
Laboratory for Yeast Molecular and Cell Biology, The Research Center of Fermentation Technology, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, Shandong, China.
FEMS Yeast Res. 2019 May 1;19(3). doi: 10.1093/femsyr/foz033.
Cdc50 is the non-catalytic subunit of the flippase that establishes phospholipid asymmetry in membranes and functions in vesicle-mediated trafficking in Saccharomyces cerevisiae. Here, we have identified the homologous gene CaCDC50 that encodes a protein of 396 amino acids with two conserved transmembrane domains in Candidaalbicans. Deletion of CaCDC50 results in C. albicans cells becoming sensitive to the antifungal drugs azoles, terbinafine and caspofungin, as well as to the membrane-perturbing agent sodium dodecyl sulfate. We also show that CaCDC50 is involved in both endocytosis and vacuolar function. CaCDC50 confers tolerance to high concentrations of cations, although it is not required for osmolar response. Moreover, deletion of CaCDC50 leads to severe defects in hyphal development of C. albicans cells and highly attenuated virulence in the mouse model of systemic infection. Therefore, CaCDC50 regulates cellular responses to antifungal drugs, cell membrane stress, endocytosis, filamentation and virulence in the human fungal pathogen C. albicans.
Cdc50 是非翻转酶的非催化亚基，在膜中建立磷脂不对称性，并在酵母 Saccharomyces cerevisiae 的囊泡介导运输中发挥作用。在这里，我们已经鉴定出同源基因 CaCDC50，该基因编码一个由 396 个氨基酸组成的蛋白质，在 Candidaalbicans 中有两个保守的跨膜结构域。CaCDC50 的缺失导致 C. albicans 细胞对唑类、特比萘芬和卡泊芬净等抗真菌药物以及十二烷基硫酸钠等膜扰动剂敏感。我们还表明 CaCDC50 参与内吞作用和液泡功能。CaCDC50 赋予细胞对高浓度阳离子的耐受性，尽管它不是渗透压反应所必需的。此外，CaCDC50 的缺失导致 C. albicans 细胞菌丝发育严重缺陷，并在系统性感染的小鼠模型中毒力显著降低。因此，CaCDC50 调节人源真菌病原体 C. albicans 中细胞对抗真菌药物、细胞膜应激、内吞作用、丝状生长和毒力的反应。
