Fig. 3.

The Ca²⁺/calcineurin pathway and Ras-signaling pathway in C. neoformans. These two pathways are also involved in a variety of stress responses, including thermotolerance and pheromone-responsive mating. Calmodulin (Cam1) binds four Ca²⁺ molecules via four EF hand motifs. Subsequently, Ca²⁺-bound Cam1 activates calcineurin, a complex composed of a catalytic subunit A and a regulatory subunit B. Cyclophilin A and FK506-binding protein (FKBP12) bound with CsA and FK506, respectively, inhibit the activation of calcineurin. The Ras-signaling pathway governs thermotolerance in a Cdc24 (a guanine nucleotide exchange factor) and Cdc42 (GTPase)-dependent manner. Ras1 and Ras2 share some functions in both thermotolerance and mating.