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Spatially Distinct Pools of TORC1 Balance Protein Homeostasis.
- Source :
-
Molecular cell [Mol Cell] 2019 Jan 17; Vol. 73 (2), pp. 325-338.e8. Date of Electronic Publication: 2018 Dec 06. - Publication Year :
- 2019
-
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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Adaptor Proteins, Signal Transducing metabolism
Autophagy
Autophagy-Related Proteins genetics
Autophagy-Related Proteins metabolism
Endosomal Sorting Complexes Required for Transport genetics
Endosomal Sorting Complexes Required for Transport metabolism
Endosomes enzymology
Endosomes genetics
Gene Expression Regulation, Fungal
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases metabolism
Proteolysis
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae Proteins genetics
Signal Transduction
Transcription Factors genetics
Vacuoles enzymology
Vacuoles genetics
Proteostasis
Saccharomyces cerevisiae enzymology
Saccharomyces cerevisiae Proteins metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 73
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 30527664
- Full Text :
- https://doi.org/10.1016/j.molcel.2018.10.040