Figure 11.

Proposed roles of the calcineurin signaling cascade in stress responses, drug tolerance, and virulence in C. glabrata. Calcineurin and Crz1 are required for various stress responses, including thermotolerance, ER stress, echinocandin tolerance, cell membrane integrity, and virulence. Calcineurin also exhibits Crz1-independent functions, including pH homeostasis and optimal growth in serum. Calcineurin (Cna1 or Cnb1) suppresses calcium tolerance, whereas Crz1 inhibits azole tolerance. Regulator of calcineurin 1 (Rcn1) is an endogenous positive regulator of calcineurin that participates in the control of multiple cellular processes, including thermotolerance, ER stress, and echinocandin tolerance. Rcn2 acts as a feedback inhibitor of calcineurin function in calcium tolerance. Solid arrows represent promoting functions, and bar-headed arrows represent inhibitory functions within the calcineurin signaling cascade. The dotted arrow represents function as seen in S. cerevisiae, but undetermined in C. glabrata.