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 language | English |
|---|---|
| Pages (from-to) | 325-338.e8 |
| Number of pages | 23 |
| Journal | Molecular Cell |
| Volume | 73 |
| Issue number | 2 |
| Early online date | 6 Dec 2018 |
| DOIs | |
| Publication status | Published - 17 Jan 2019 |
Bibliographical note
We thank Laurent Falquet for the bioinformatic analyses of the whole genome sequences, Benjamin Pillet for help with assembling Figure 5A, and Yoshinori Ohsumi, Takeshi Noda, Scott Emr, Robbie Loewith, and BIOSS Toolbox (University of Freiburg) for plasmids and/or strains. This research was supported by the Canton of Fribourg and the Swiss National Science Foundation (J.D. and C.D.V.).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
