Abstract
The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.
Highlights
The conserved target of rapamycin (TOR) signaling pathway controls cell growth and proliferation across taxa and disease states by regulating metabolic processes in response to available nutrients and energy [1,2,3,4]
BLAST analysis suggests the 522 amino acid Abl1 protein carries an N-terminal glycogen-binding domain (GBD) that is associated with the catalytic domain of AMPK β subunits, but lacks the iteration domain carried by canonical AMPK β subunits such as the M. oryzae MoSip2 protein [32]
ABL1 expression was downregulated 9-fold in wild type (WT) when grown under glucose starvation conditions compared to growth on glucose minimal media (GMM) with nitrate, and was downregulated 25-fold in Δtps1 mutant strains compared to WT on GMM with nitrate (Fig 1A)
Summary
The conserved TOR signaling pathway controls cell growth and proliferation across taxa and disease states by regulating metabolic processes in response to available nutrients and energy [1,2,3,4]. TORC1 is rapamycin sensitive and exerts temporal control on cell growth by regulating ribosome biogenesis in addition to protein, lipid and nucleotide biosynthesis. Loss of TORC1 components, or rapamycin treatment, results in cell cycle arrest at G1/G0 [1,12,13] and autophagy induction [1,14]. Temperature-sensitive yeast Kog mutants have shown that under nutrient-poor or rapamycin treatment conditions, TORC1 first delays the cell cycle at G2/M and induces autophagy before progressing mitosis to G1/G0 arrest [11, 14]
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