Crosstalk between Ras and inositol phosphate signaling revealed by lithium action on inositol monophosphatase in Schizophyllum commune

Abstract

Mushroom forming basidiomycete Schizophyllum commune has been used as a tractable model organism to study fungal sexual development. Ras signaling activation via G-protein-coupled receptors (GPCRs) has been postulated to play a significant role in the mating and development of S. commune . In this study, a crosstalk between Ras signaling and inositol phosphate signaling by inositol monophosphatase (IMPase) is revealed. Constitutively active Ras1 leads to the repression of IMPase transcription and lithium action on IMPase activity is compensated by the induction of IMPase at transcriptome level. Astonishingly, in S. commune lithium induces a considerable shift to inositol phosphate metabolism leading to a massive increase in the level of higher phosphorylated inositol species up to the inositol pyrophosphates. The lithium induced metabolic changes are not observable in a constitutively active Ras1 mutant. In addition to that, proteome profile helps us to elucidate an overview of lithium action to the broad aspect of fungal metabolism and cellular signaling. Taken together, these findings imply a crosstalk between Ras and inositol phosphate signaling.

From mine to mind and mobiles – Lithium contamination and its risk management

“…Lithium also affects plant metabolism in different organelles (e.g., mitochondria, peroxisomes, and chloroplasts) (Qiao et al, 2018), and its impact is considered non-specific because Li is able to substitute other important monovalent cations (e.g., Na + , K + ) in plant cells (Kabata-Pendias and Mukherjee, 2007). Lithium inhibits inositol monophosphatases and calcium signalling at high concentrations by interfering with the activity of inositol monophosphatases and dephosphorylation of inositol-1-phosphate (Baran, 2019, Murry et al, 2019.…”

Response of the wood-decay fungus Schizophyllum commune to co-occurring microorganisms

“…Among the identified signaling molecules, 1-phosphatidyl-D-myo-inositol was formed. Recently, inositol phosphate signaling in S. commune has been found to be linked to morphogenesis by signal transfer from the pheromone receptor to the central regulator, the monomeric G-protein Ras [45]. With respect to biotic interactions, host virulence in cryptococcal disease [46] had been linked to the inositol phosphate cycle that also regulates chemotaxis of Dictyostelium discoideum [47].…”

Fungal Kinases With a Sweet Tooth: Pleiotropic Roles of Their Phosphorylated Inositol Sugar Products in the Pathogenicity of Cryptococcus neoformans Present Novel Drug Targeting Opportunities

“…Future work in fungal pathogenesis needs to address whether, and which, transcription factors respond to IPs, and how IPs regulate virulence-related signaling pathways, including the PHO pathway. Crosstalk between IPs and Ras signaling has been reported in the basidiomycete, Schizophyllum commune , where lithium-induced activation of the IPK pathway, leading to increased levels of PP-IPs, was not observed in a Ras1 mutant (Murry et al, 2019).…”