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.
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Protein | Site | Modification | Modifier |
|---|---|---|---|
| VPS27 | S155 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
| VPS27 | S157 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
| VPS27 | T159 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
| VPS27 | S274 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
| VPS27 | S277 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
| VPS27 | S279 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
| VPS27 | S280 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
| VPS27 | S339 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
| VPS27 | S494 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
| VPS27 | S495 | phosphorylated residue | TORC1 serine/threonine-protein kinase complex, TOR1 variant |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.