Tsao Chang-Chih, Chen Yu-Ting, Lan Chung-Yu
Institute of Molecular and Cellular Biology, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan, ROC.
Fungal Genet Biol. 2009 Feb;46(2):126-36. doi: 10.1016/j.fgb.2008.11.008. Epub 2008 Dec 6.
Rheb is a new member of the small G proteins of the Ras superfamily in eukaryotic organisms and controls various physiological processes. Activity of Rheb is regulated by Tsc2, a GTPase-activating protein (GAP). In this study, we have identified Candida albicans homologs of Rheb (named as Rhb1) and Tsc2. Deletion of the RHB1 gene showed enhanced sensitivity to rapamycin (an inhibitor of TOR kinase), suggesting that Rhb1 is associated with the TOR signaling pathway in C. albicans. Further analysis indicated RHB1 and TSC2 are involved in nitrogen starvation-induced filamentation, likely by controlling the expression of MEP2 whose gene product is an ammonium permease and a sensor for the nitrogen signal. Moreover, we have demonstrated that Rhb1 is also involved in cell wall integrity pathway, by transferring signals through the TOR kinase and the Mkc1 MAP kinase pathway. Together, this study brings new insights into the complex interplay of signaling and regulatory pathways in C. albicans.
Rheb是真核生物中Ras超家族小G蛋白的新成员，可控制各种生理过程。Rheb的活性受GTP酶激活蛋白（GAP）Tsc2的调节。在本研究中，我们鉴定了白色念珠菌中Rheb（命名为Rhb1）和Tsc2的同源物。RHB1基因的缺失显示出对雷帕霉素（一种TOR激酶抑制剂）的敏感性增强，这表明Rhb1与白色念珠菌中的TOR信号通路相关。进一步分析表明，RHB1和TSC2可能通过控制MEP2的表达参与氮饥饿诱导的菌丝形成，MEP2的基因产物是一种铵通透酶和氮信号传感器。此外，我们已经证明，Rhb1还通过TOR激酶和Mkc1 MAP激酶途径传递信号，参与细胞壁完整性途径。总之，这项研究为白色念珠菌信号传导和调节途径的复杂相互作用带来了新的见解。
