SakA and MpkC Stress MAPKs Show Opposite and Common Functions During Stress Responses and Development in Aspergillus nidulans

Abstract

Stress activated MAP kinases (SAPKs) of the Hog1/Sty1/p38 family are specialized in transducing stress signals. In contrast to what is seen in animal cells, very few fungal species contain more than one SAPK. Aspergillus nidulans and other Aspergilli contain two SAPKs called SakA/HogA and MpkC. We have shown that SakA is essential for conidia to maintain their viability and to survive high H2O2 concentrations. H2O2 induces SakA nuclear accumulation and its interaction with transcription factor AtfA. Although SakA and MpkC show physical interaction, little is known about MpkC functions. Here we show that ΔmpkC mutants are not sensitive to oxidative stress but in fact MpkC inactivation partially restores the oxidative stress resistance of ΔsakA mutants. ΔmpkC mutants display about twofold increase in the production of fully viable conidia. The inactivation of the SakA upstream MAPKK PbsB or the simultaneous elimination of sakA and mpkC result in virtually identical phenotypes, including decreased radial growth, a drastic reduction of conidiation and a sharp, progressive loss of conidial viability. SakA and to a minor extent MpkC also regulate cell-wall integrity. Given the roles of MpkC in conidiation and oxidative stress sensitivity, we used a functional MpkC::GFP fusion to determine MpkC nuclear localization as an in vivo indicator of MpkC activation during asexual development and stress. MpkC is mostly localized in the cytoplasm of intact conidia, accumulates in nuclei during the first 2 h of germination and then becomes progressively excluded from nuclei in growing hyphae. In the conidiophore, MpkC nuclear accumulation increases in vesicles, metulae and phialides and decreases in older conidia. Oxidative and osmotic stresses induce MpkC nuclear accumulation in both germinating conidia and hyphae. In all these cases, MpkC nuclear accumulation is largely dependent on the MAPKK PbsB. Our results indicate that SakA and MpkC play major, distinct and sometimes opposing roles in conidiation and conidiospore physiology, as well as common roles in response to stress. We propose that two SAPKs are necessary to delay (MpkC) or fully stop (SakA) mitosis during conidiogenesis and the terminal differentiation of conidia, in the highly prolific phialoconidiation process characteristic of the Aspergilli.

Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in Aspergillus fumigatus

“…This hypothesis is corroborated by the fact that A. nidulans SakA and MpkC not only physically interact, but also show opposite and common functions during stress responses and development (51, 52).…”

DnmA and FisA Mediate Mitochondria and Peroxisome Fission, and Regulate Mitochondrial Function, ROS Production and Development in Aspergillus nidulans

“…There is strong evidence showing that ROS regulate fungal development (Hansberg and Aguirre, 1990;Lara-Ortiz et al, 2003;Aguirre et al, 2005;Cano-Dominguez et al, 2008Lara-Rojas et al, 2011;Mendoza-Martinez et al, 2017;Garrido-Bazan et al, 2018). We have shown that mitochondrial division is critically associated to fungal development and ROS production and that mitochondrial division is in turn regulated by ROS.…”

“…In one approach, we have used the filamentous fungi Aspergillus nidulans to study the mechanisms by which cells perceive and respond to external ROS. In this and other fungi, the SakA-MpkC stress MAPK pathway plays crucial roles in responding to multiple types of stress, including oxidative stress (Kawasaki et al, 2002;Lara-Rojas et al, 2011;Garrido-Bazan et al, 2018). During the course of that work, we found that the MAPKAP-kinase SrkA is part of this pathway and that in response to external H 2 O 2 it translocates from the cytoplasm to either the nucleus or the mitochondria, depending on the presence of the upstream MAPK SakA.…”

Red- and Blue-Light Sensing in the Plant Pathogen Alternaria alternata Depends on Phytochrome and the White-Collar Protein LreA

“…An important player in red-light regulation and stress signaling in A. nidulans is the HOG MAP kinase SakA (38, 61, 67). There is also evidence for a link between blue-light signaling and the transcriptional and posttranslational regulation of the MAP kinase Tmk3 in Trichoderma atroviride and in N.…”