Multiple roles and diverse regulation of the Ras/cAMP/protein kinase A pathway in Candida albicans

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.