Spatially distinct pools of TORC1 balance protein homeostasis
- Hatakeyama, Riko Department of Biology, University of Fribourg, Switzerland
- Péli-Gulli, Marie-Pierre Department of Biology, University of Fribourg, Switzerland
- Hu, Zehan Department of Biology, University of Fribourg, Switzerland
- Jaquenoud, Malika Department of Biology, University of Fribourg, Switzerland
- Osuna, Guillermo Miguel Garcia Department of Biology, University of Fribourg, Switzerland
- Sardu, Alessandro Department of Biology, University of Fribourg, Switzerland
- Dengjel, Jörn Department of Biology, University of Fribourg, Switzerland - Department of Dermatology, Medical Center, University of Freiburg, Germany
- De Virgilio, Claudio Department of Biology, University of Fribourg, Switzerland
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17.01.2019
Published in:
- Molecular Cell. - 2019, vol. 73, no. 2, p. 325-338.e8
English
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
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 324097
- DOI 10.1016/j.molcel.2018.10.040
- Persistent URL
- https://folia.unifr.ch/unifr/documents/307478
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