State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
Mol Microbiol. 2019 Jan;111(1):6-16. doi: 10.1111/mmi.14148. Epub 2018 Nov 4.
Candida albicans is a major fungal pathogen of humans, causing both superficial and life-threatening systemic infections in immunocompromised people. The conserved Ras/cAMP/PKA pathway plays a key role in regulating multiple traits important for the virulence of C. albicans such as cell growth, yeast-hyphal transition, white-opaque switching, sexual reproduction and biofilm development. Diverse external signals influence cell physiology by activating this signaling pathway. The key components of the Ras/cAMP/PKA pathway include two Ras GTPases (Ras1 and Ras2), an adenylyl cyclase (Cyr1, also known as Cdc35), two cyclic nucleotide phosphodiesterases (Pde1 and Pde2) and the catalytic (Tpk1 and Tpk2) and regulatory (Bcy1) subunits of PKA kinase. Activation of this pathway dramatically alters the gene expression profile via several transcription factors, leading to the activation of specific biological processes. Here, we review the progress made in the past two decades to elucidate the molecular mechanisms by which the Ras/cAMP/PKA pathway senses diverse environmental cues and controls specific cellular responses and its connection with other signaling pathways in C. albicans.
白色念珠菌是一种重要的人类真菌病原体，在免疫功能低下的人群中可引起浅表性和危及生命的全身性感染。保守的 Ras/cAMP/PKA 途径在调节白色念珠菌毒力的多个重要特征方面发挥着关键作用，如细胞生长、酵母-菌丝过渡、白-暗相转换、有性生殖和生物膜形成。多种外部信号通过激活该信号通路来影响细胞生理学。Ras/cAMP/PKA 途径的关键组成部分包括两个 Ras GTPases（Ras1 和 Ras2）、一个腺苷酸环化酶（Cyr1，也称为 Cdc35）、两个环核苷酸磷酸二酯酶（Pde1 和 Pde2）以及 PKA 激酶的催化（Tpk1 和 Tpk2）和调节（Bcy1）亚基。该途径的激活通过几个转录因子极大地改变了基因表达谱，导致特定生物过程的激活。在这里，我们回顾了过去二十年在阐明 Ras/cAMP/PKA 途径如何感知不同环境线索并控制特定细胞反应的分子机制方面取得的进展，以及它与白色念珠菌中其他信号通路的联系。
