Fig 1.

Calcineurin signaling in fungal pathogens. Calcineurin signaling is initiated upon calcium influx and binding of calcium-calmodulin (CaM) to the calcineurin complex (CNA and CNB). The binding of CaM releases an autoinhibitory domain that occupies the active site in the catalytic subunit CNA converting calcineurin from an inactive “OFF” configuration to a fully active “ON” state. Upon activation, calcineurin dephosphorylates its substrates, which include a conserved transcription factor, Crz1, and several others that remain unidentified in most fungal species. Through these targets, calcineurin governs stress responses, morphological transitions, and virulence in fungal pathogens of humans and plants. As described in the right-side panel, calcineurin directs yeast–hyphal dimorphic transitions in some fungi, whereas it is required for vegetative yeast or hyphal growth in other fungal species. In some cases, calcineurin orchestrates the development of specialized structures, such as formation of appressoria in M. oryzae, that are required for infection and virulence. Calcineurin activity can be inhibited by FK506 and cyclosporine (CsA), both of which are immunosuppressive drugs when bound to FKBP12 or cyclophilin A (Cyp). The figure was created with BioRender.com.