Fig. 5

Simplified schematic depiction of the major signalling cascades in filamentous fungal cell factories. MAPK cascades are initiated at the plasma membrane by two main processes. Firstly, a G protein’s α subunit activates a protein activated kinase (PAK), which phosphorylates an MAPKKK. Secondly, in the two-component signal transduction system, a transmembrane histidine kinase (HK) is activated by extracellular ligands and a response regulator (REG) activates a histidine-containing phospho-transmitter (HP) that subsequently activates MAPK signalling. Alternatively, mechanosensors such as WSC receptors [104] at the cell surface are activated by cell wall perturbation, which activate MAPK cascades via GTPases (e.g. Rho1) and protein kinase C (PkcA). Once active, a phosphorelay system between MAPKKK, MAPKK and MAPK results in phosphorylation of downstream transcription factors. In the PKA/cAMP pathway, a G-protein coupled receptor (GPCR) is activated at the plasma membrane and ultimately the G protein’s α subunit (α-sub) dissociates from the GPCR complex and activates an adenylyl cyclase (AC). This, in turn, catalyses the conversion of ATP into cAMP. Increases in concentration of the second messenger cAMP activates protein kinase A (PKA), which phosphorylates various target proteins, including transcription factors. These enter the nucleus and regulate diverse responses. In calcium signalling, low- and high-affinity Ca²⁺ influx systems are activated at the plasma membrane. Ca²⁺ ions bind and activate calmodulin (CaM), which in turn binds to subunit A of the protein calcineurin (CnaA). Once activated, calcineurin dephosphorylates the transcription factor CrzA, which causes elevated expression of genes necessary for growth and diverse stress responses. Depicted are exemplar transcription factors that regulate filamentous growth (BrlA, StuA, FlbA, CrzA), cell wall integrity (CrzA, MsnA, RlmA), adaption to carbon limitation (CreA) and nitrogen limitation (AreA). All pathways have critical control of filamentous growth, fungal morphology, and development. Gene names are taken from A. niger or the model organism A. nidulans. Note that extensive cross talk occurs between pathways, and that in this schematic not all possible membrane receptors, signalling proteins, or transcription factors are depicted. Interested readers are guided to excellent reviews which cover fungal signalling cascades in greater depth ([91, 118])