Department of Biotechnology, Center for Fungal Pathogenesis, Yonsei University, Seoul, Republic of Korea.
Fungal Genet Biol. 2011 Feb;48(2):154-65. doi: 10.1016/j.fgb.2010.10.006. Epub 2010 Oct 28.
The mitogen-activated protein kinase (MAPK) pathways control diverse cellular functions in pathogenic fungi, including sexual differentiation, stress response, and maintenance of cell wall integrity. Here we characterized a Cryptococcus neoformans gene, which is homologous to the yeast Ste50 that is known to play an important role in mating pheromone response and stress response as an adaptor protein to the Ste11 MAPK kinase kinase in Saccharomyces cerevisiae. The C. neoformans Ste50 was not involved in any of the stress responses or virulence factor production (capsule and melanin) that are controlled by the HOG and Ras/cAMP signaling pathways. However, Ste50 was required for mating in both serotype A and serotype D C. neoformans strains. The ste50Δ mutant was completely defective in cell-cell fusion and mating pheromone production. Double mutation of the STE50 gene blocked increased production of pheromone and the hyper-filamentation phenotype of cells deleted of the CRG1 gene, which encodes the RGS protein that negatively regulates pheromone responsive G-protein signaling via the MAPK pathway. Regardless of the presence of the basidiomycota-specific SH3 domains of Ste50 that are known to be required for full virulence of Ustilago maydis, Ste50 was dispensable for virulence of C. neoformans in a murine model of cryptococcosis. In conclusion, the Ste50 adaptor protein controls sexual differentiation of C. neoformans via the pheromone-responsive MAPK pathway but is not required for virulence.
丝裂原活化蛋白激酶（MAPK）途径控制病原真菌中的多种细胞功能，包括有性分化、应激反应和细胞壁完整性的维持。在这里，我们描述了一种新型隐球菌基因，该基因与酵母 Ste50 同源，已知 Ste50 作为酵母 Ste11 MAPK 激酶激酶的衔接蛋白，在交配信息素反应和应激反应中发挥重要作用。新型隐球菌 Ste50 不参与任何应激反应或毒力因子的产生（荚膜和黑色素），这些过程是由 HOG 和 Ras/cAMP 信号通路控制的。然而，Ste50 参与了 A 型和 D 型新型隐球菌菌株的交配。ste50Δ突变体在细胞融合和交配信息素产生方面完全缺失。STE50 基因的双突变阻断了信息素产量的增加和 CRG1 基因缺失细胞的过度丝状化表型，CRG1 基因编码的 RGS 蛋白通过 MAPK 途径负调控信息素响应 G 蛋白信号。无论 Ste50 中是否存在已知对 Ustilago maydis 完全毒力所必需的担子菌类特异性 SH3 结构域，Ste50 在新型隐球菌的小鼠隐球菌病模型中对毒力都是可有可无的。总之，Ste50 衔接蛋白通过信息素反应性 MAPK 途径控制新型隐球菌的有性分化，但不参与毒力。
