The Activators of Type 2A Phosphatases (PP2A) Regulate Multiple Cellular Processes Via PP2A-Dependent and -Independent Mechanisms in Fusarium graminearum

Abstract

The type 2A protein phosphatases (PP2As) are holoenzymes in all eukaryotes but their activators remain unknown in filamentous fungi. Fusarium graminearum contains three PP2As (FgPp2A, FgSit4, and FgPpg1), which play critical roles in fungal growth, development, and virulence. Here, we identified two PP2A activators (PTPAs), FgRrd1 and FgRrd2, and found that they control PP2A activity in a PP2A-specific manner. FgRrd1 interacts with FgPpg1, but FgRrd2 interacts with FgPp2A and very weakly with FgSit4. Furthermore, FgRrd2 activates FgPp2A via regulating FgPp2A methylation. Phenotypic assays showed that FgRrd1 and FgRrd2 regulate mycelial growth, conidiation, sexual development, and lipid droplet biogenesis. More importantly, both FgRrd1 and FgRrd2 interact with RNA polymerase II, subsequently modulating its enrichments at the promoters of mycotoxin biosynthesis genes, which is independent on PP2A. In addition, FgRrd2 modulates response to phenylpyrrole fungicide, via regulating the phosphorylation of kinase FgHog1 in the high-osmolarity glycerol pathway, and to caffeine, via modulating FgPp2A methylation. Taken together, results of this study indicate that FgRrd1 and FgRrd2 regulate multiple physiological processes via different regulatory mechanisms in F. graminearum, which provides a novel insight into understanding the biological functions of PTPAs in fungi.

Genomic Identification of the TOR Signaling Pathway as a Target of the Plant Alkaloid Antofine in the Phytopathogen Fusarium graminearum

“…graminearum (FGSG_07174) with 73% identity, and the ScRRD1 gene (resistant to rapamycin deletion 1; YIL153W) has two homologues in F. graminearum, FGSG_09229 ( FgRRD1 ) and FGSG_01092 ( FgRRD2 ), with identities of 38 and 32%, respectively (13). The third target identified in yeast YBR095C showed a weak homology (18% identity) with F.…”

“…Inhibition of TOR signaling by rapamycin, which binds Fkbp12 to inhibit Tor kinase and the downstream Tap42 protein phosphatase complex, reduces both vegetative growth and conidial germination, leading to reduced pathogenicity (11). In addition, two peptidyl-proly cis / trans -isomerases, RRD1 (FGSG_09229) and RRD2 (FGSG_01092), which regulate the activity of type 2A phosphatases of the TOR pathway and confer resistance to rapamycin when mutated (12), have overlapping functions in mycotoxin production and virulence, as well as growth and reproduction (13). However, the severity of growth defects and asexual spore production are more pronounced in the F.…”

“…However, the severity of growth defects and asexual spore production are more pronounced in the F. graminearum rrd2 ( Fgrrd2 ) mutant than Fgrrd1 (13). In addition, Fg RRD2, but not Fg RRD1, modulates sensitivity to the phenylpyrrole fungicide fludioxonil and plays a dominant role in regulation of the high-osmolarity glycerol (HOG) pathway in F.…”

“…In addition, Fg RRD2, but not Fg RRD1, modulates sensitivity to the phenylpyrrole fungicide fludioxonil and plays a dominant role in regulation of the high-osmolarity glycerol (HOG) pathway in F. graminearum (13).…”

Analysis of the inhibitory effect of rapamycin on <i>Fusarium asiaticum</i> by next generation RNA sequencing

“…In S. cerevisiae it is known that deletion of Ppg1 has no obvious effect on cell growth 38) . However, in F. graminearum, deficiency of FaPpg1 causes various defects, including reduction of mycelium proliferation and impairment of asexual reproduction and sexual development 39) . In F. asiaticum, the significance of FaPpg1 is still unknown.…”