Two Rac paralogs regulate polarized growth in the human fungal pathogen Cryptococcus neoformans.

Two Rac paralogs regulate polarized growth in the human fungal pathogen Cryptococcus neoformans.
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DOI:
10.1016/j.fgb.2013.05.006
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发表时间:
2013-08
影响因子:
3
通讯作者:
Alspaugh, J. Andrew
Alspaugh, J. Andrew
中科院分区:
生物学3区
文献类型:
--
作者:
Ballou, Elizabeth Ripley;Selvig, Kyla;Narloch, Jessica L.;Nichols, Connie B.;Alspaugh, J. Andrew

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人类真菌病原体新型隐球菌变种的全基因组分析。Grubii揭示了许多与形态发生有关的高度保守基因的重复。以前,我们报道了重复Cdc 42旁系同源物提供C。对环境胁迫具有生态位特异性反应的新形虫:Cdc 42是耐热性所需的,而Cdc 420支持泰坦细胞的形成。相关的Rho-GTdR Rac 1已在C.新形变种新生儿在表达中起主要作用,并共享Cdc 42/Cdc 420结合伴侣。在这里,我们报告的第二个Rac parasites在C。neoformans,Rac 2,并描述了其与先前描述的CnRac,Rac 1的重叠功能。此外,我们表明,Rac旁系同源物通过组织活性氧在极化生长中发挥主要作用,在肌动蛋白的组织中只发挥次要作用。最后,我们提供了初步的证据表明,Rac活性和肌动蛋白稳定性的药理学抑制剂具有协同活性。
A genome wide analysis of the human fungal pathogen Cryptococcus neoformans var. grubii has revealed a number of duplications of highly conserved genes involved in morphogenesis. Previously, we reported that duplicate Cdc42 paralogs provide C. neoformans with niche-specific responses to environmental stresses: Cdc42 is required for thermotolerance, while Cdc420 supports the formation of titan cells. The related Rho-GTPase Rac1 has been shown in C. neoformans var. neoformans to play a major role in filamentation and to share Cdc42/Cdc420 binding partners. Here we report the characterization of a second Rac paralog in C. neoformans, Rac2, and describe its overlapping function with the previously described CnRac, Rac1. Further, we demonstrate that the Rac paralogs play a primary role in polarized growth via the organization of reactive oxygen species and play only a minor role in the organization of actin. Finally, we provide preliminary evidence that pharmacological inhibitors of Rac activity and actin stability have synergistic activity.
DOI: 10.1073/pnas.91.2.619
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