The PP2A regulatory subunits, Cdc55 and Rts1, play distinct roles in Candida albicans' growth, morphogenesis, and virulence
The PP2A regulatory subunits, Cdc55 and Rts1, play distinct roles in Candida albicans' growth, morphogenesis, and virulence
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DOI：
10.1016/j.fgb.2019.103240
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发表时间：
2019-10-01
影响因子：
3
通讯作者：
Sang, Jianli
中科院分区：
文献类型：
--
作者：
Han, Qi;Pan, Chaoying;Sang, Jianli
蛋白磷酸酶-2A（PP 2A）是由催化亚基、调节亚基和结构亚基组成的异源三聚体酶。在白色念珠菌中，Cdc 55和Rts 1被鉴定为可能的PP 2A的调节亚基，其含有催化亚基Pph 21和结构亚基Tpd 3。Tpd 3-Pph 21磷酸酶调节细胞形态发生和分裂。然而，Cdc 55和Rts 1的功能尚不清楚。在这里，我们构建了cdc 55 Delta/Delta和rts 1 Delta/Delta突变体，发现它们在多种表型中表现出不同的缺陷，尽管两者都表现出类似的septin Sep 7过度磷酸化和异常septin组织。在酵母生长条件下，cdc 55 Delta/Delta突变体作为假菌丝缓慢生长，其中一些细胞缺乏细胞核，而rts 1 Delta/Delta细胞是圆形和扩大的，似乎经历了不完全的细胞分离，产生多核细胞。强烈的几丁质沉积发生在cdc 55 Delta/Delta细胞的隔膜和rts 1 Delta/Delta细胞的表面上，这可能有助于增加对卡泊芬净的敏感性。此外，cdc 55 Delta/Delta在菌丝和生物膜形成方面表现出严重缺陷，而rts 1 Delta/Delta是部分缺陷的。这两种突变体在小鼠中的毒力都有所降低，表明PP 2A-B亚基可以作为潜在的抗真菌靶点。
Protein phosphatase-2A (PP2A) is a heterotrimeric enzyme composed of a catalytic subunit, a regulatory subunit, and a structural subunit. In Candida albicans, Cdc55 and Rts1 have been identified as possible regulatory subunits of PP2A containing the catalytic subunit Pph21 and structural subunit Tpd3. The Tpd3-Pph21 phosphatase regulates cell morphogenesis and division. However, the functions of Cdc55 and Rts1 remain unclear. Here, we constructed cdc55 Delta/Delta and rts1 Delta/Delta mutants and found that they exhibit different defects in multiple phenotypes although both show similar hyperphosphorylation of the septin Sep7 and aberrant septin organization. Under yeast growth conditions, the cdc55 Delta/Delta mutant grows slowly as pseudohyphae with some cells lacking the nucleus, while rts1 Delta/Delta cells are round and enlarged and seem to undergo incomplete cell separation producing multinucleated cells. Strong chitin deposition occurs at the septum of cdc55 Delta/Delta cells and on the surface of rts1 Delta/Delta cells, which likely contributes to increased susceptibility to caspofungin. Also, cdc55 Delta/Delta exhibits severe defects in hyphal and biofilm formation, while rts1 Delta/Delta is partially defective. Both mutants show reduced virulence in mice, suggesting that PP2A-B subunits could serve as potential antifungal targets.