A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans

Lenka Halova, David Cobley, Mirita Franz-wachtel, Tingting Wang, Kaitlin R Morrison, Karsten Krug, Nicolas Nalpas, Boris Macek, Iain M. Hagan, Sean J Humphrey, Janni Petersen

    Research output: Contribution to journalArticlepeer-review

    1 Downloads (Pure)

    Abstract

    Fluctuations in TOR, AMPK and MAP-kinase signalling maintain cellular homeostasis and coordinate growth and division with environmental context. We have applied quantitative, SILAC mass spectrometry to map TOR and nutrient-controlled signalling in the fission yeast Schizosaccharomyces pombe. Phosphorylation levels at more than 1000 sites were altered following nitrogen stress or Torin1 inhibition of the TORC1 and TORC2 networks that comprise TOR signalling. One hundred and thirty of these sites were regulated by both perturbations, and the majority of these (119) new targets have not previously been linked to either nutritional or TOR control in either yeasts or humans. Elimination of AMPK inhibition of TORC1, by removal of AMPKα (ssp2::ura4+), identified phosphosites where nitrogen stress-induced changes were independent of TOR control. Using a yeast strain with an ATP analogue-sensitized Cdc2 kinase, we excluded sites that were changed as an indirect consequence of mitotic control modulation by nitrogen stress or TOR signalling. Nutritional control of gene expression was reflected in multiple targets in RNA metabolism, while significant modulation of actin cytoskeletal components points to adaptations in morphogenesis and cell integrity networks. Reduced phosphorylation of the MAPKK Byr1, at a site whose human equivalent controls docking between MEK and ERK, prevented sexual differentiation when resources were sparse but not eliminated.

    Original languageEnglish
    Article number200405
    Number of pages1
    JournalOpen Biology
    Volume11
    Issue number4
    DOIs
    Publication statusPublished - 1 Apr 2021

    Keywords

    • TORC1
    • TORC2
    • nitrogen stress
    • phosphoproteome
    • fission yeast
    • Schizosaccharomyces pombe
    • Byr1 MAPKK
    • fission yeast Schizosaccharomyces pombe

    Fingerprint

    Dive into the research topics of 'A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans'. Together they form a unique fingerprint.

    Cite this