Ent2 Governs Morphogenesis and Virulence in Part through Regulation of the Cdc42 Signaling Cascade in the Fungal Pathogen Candida albicans.
Ent2 Governs Morphogenesis and Virulence in Part through Regulation of the Cdc42 Signaling Cascade in the Fungal Pathogen Candida albicans.
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作者：
在酵母和丝状生长状态之间转换的能力对于主要人类真菌病原体白色念珠菌的毒力至关重要。大规模的遗传筛选已经确定了这种形态转换所需的数百个基因，但其中许多基因协调这种发育转变的机制在很大程度上仍然难以捉摸。在这项研究中，我们描述了Ent 2在C.白色念珠菌我们发现，Ent 2是需要在广泛的诱导条件下的丝状生长，也需要在小鼠模型的系统性念珠菌病的毒力。我们发现，epsin N-末端同源性（ENTH）结构域的Ent 2使形态和毒力，并通过与Cdc 42 GTP酶激活蛋白（GAP）Rga 2和调节其本地化的物理相互作用。进一步的分析表明，Cdc 42效应蛋白Cla 4的过表达可以克服ENTH-Rga 2物理相互作用的需要，表明Ent 2的功能，至少部分地，使Cdc 42-Cla 4信号通路的适当激活的存在下，诱导的线索。总的来说，这项工作的特点是Ent 2调节菌丝形态发生在C。白念珠菌，揭示了该因子在系统性念珠菌病体内模型中使毒力的重要性，并增加了对关键毒力性状的遗传控制的日益增长的理解。
The ability to transition between yeast and filamentous growth states is critical for virulence of the leading human fungal pathogen Candida albicans. Large-scale genetic screens have identified hundreds of genes required for this morphological switch, but the mechanisms by which many of these genes orchestrate this developmental transition remain largely elusive. In this study, we characterized the role of Ent2 in governing morphogenesis in C. albicans. We showed that Ent2 is required for filamentous growth under a wide range of inducing conditions and is also required for virulence in a mouse model of systemic candidiasis. We found that the epsin N-terminal homology (ENTH) domain of Ent2 enables morphogenesis and virulence and does so via a physical interaction with the Cdc42 GTPase-activating protein (GAP) Rga2 and regulation of its localization. Further analyses revealed that overexpression of the Cdc42 effector protein Cla4 can overcome the requirement for the ENTH-Rga2 physical interaction, indicating that Ent2 functions, at least in part, to enable proper activation of the Cdc42-Cla4 signaling pathway in the presence of a filament-inducing cue. Overall, this work characterizes the mechanism by which Ent2 regulates hyphal morphogenesis in C. albicans, unveils the importance of this factor in enabling virulence in an in vivo model of systemic candidiasis and adds to the growing understanding of the genetic control of a key virulence trait.
影响因子：
4.4
作者：
Stogios, Peter J.;Liston, Sean D.;Semper, Cameron;Quade, Bradley;Michalska, Karolina;Evdokimova, Elena;Ram, Shane;Otwinowski, Zbyszek;Borek, Dominika;Cowen, Leah E.;Savchenko, Alexei
通讯作者：
Savchenko, Alexei