Spatially Distinct Pools of TORC1 Balance Protein Homeostasis

Riko Hatakeyama, Marie-Pierre Péli-Gulli, Zehan Hu, Malika Jaquenoud, Guillermo Miguel Garcia Osuna, Alessandro Sardu, Jörn Dengjel, Claudio De Virgilio* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The eukaryotic TORC1 kinase is a homeostatic controller of growth that integrates nutritional cues and mediates signals primarily from the surface of lysosomes or vacuoles. Amino acids activate TORC1 via the Rag GTPases that combine into structurally conserved multi-protein complexes such as the EGO complex (EGOC) in yeast. Here we show that Ego1, which mediates membrane-anchoring of EGOC via lipid modifications that it acquires while traveling through the trans-Golgi network, is separately sorted to vacuoles and perivacuolar endosomes. At both surfaces, it assembles EGOCs, which regulate spatially distinct pools of TORC1 that impinge on functionally divergent effectors: vacuolar TORC1 predominantly targets Sch9 to promote protein synthesis, whereas endosomal TORC1 phosphorylates Atg13 and Vps27 to inhibit macroautophagy and ESCRT-driven microautophagy, respectively. Thus, the coordination of three key regulatory nodes in protein synthesis and degradation critically relies on a division of labor between spatially sequestered populations of TORC1.

Original languageEnglish
Pages (from-to)325-338, e1-e8
Number of pages22
JournalMolecular Cell
Volume73
Issue number2
Early online date6 Dec 2018
DOIs
Publication statusPublished - 17 Jan 2019

Keywords

  • target of rapamycin complex 1
  • TORC1
  • Rag GTPases
  • amino acid signaling
  • growth control
  • macroautophagy
  • microautophagy
  • protein homeostasis
  • ESCRT
  • endosomal sorting complex required for transport
  • Atg13
  • Vps27

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    Hatakeyama, R., Péli-Gulli, M-P., Hu, Z., Jaquenoud, M., Garcia Osuna, G. M., Sardu, A., Dengjel, J., & De Virgilio, C. (2019). Spatially Distinct Pools of TORC1 Balance Protein Homeostasis. Molecular Cell, 73(2), 325-338, e1-e8. https://doi.org/10.1016/j.molcel.2018.10.040