TOR complex 2 (TORC2) signaling and the ESCRT machinery cooperate in the protection of plasma membrane integrity in yeast
| Autor: | Mihaela Angelova, Sebastian Eising, Florian Fröhlich, Simon Sprenger, David Teis, Christopher J. Stefan, Michael A. Widerin, Michael W. Hess, Yannick Weyer, Robbie Loewith, Verena Baumann, Oliver Schmidt |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Endosome Saccharomyces cerevisiae Repressor Mechanistic Target of Rapamycin Complex 2 macromolecular substances Biochemistry ESCRT Glycogen Synthase Kinase 3 stress 03 medical and health sciences membrane stress ORMDL family TOR complex endosomal sorting complexes required for transport (ESCRT) calcineurin membrane Molecular Biology Adenosine Triphosphatases Endosomal Sorting Complexes Required for Transport 030102 biochemistry & molecular biology biology Chemistry Kinase Endoplasmic reticulum Cell Membrane Cell Biology biology.organism_classification Sphingolipid TORC2 Cell biology endosome and Golgi-associated degradation (EGAD) mTOR complex (mTORC) 030104 developmental biology Mutation sphingolipid Signal Transduction |
| Zdroj: | Journal of Biological Chemistry The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra120.013222 |
| Popis: | The endosomal sorting complexes required for transport (ESCRT) mediate evolutionarily conserved membrane remodeling processes. Here, we used budding yeast (Saccharomyces cerevisiae) to explore how the ESCRT machinery contributes to plasma membrane (PM) homeostasis. We found that in response to reduced membrane tension and inhibition of TOR complex 2 (TORC2), ESCRT-III/Vps4 assemblies form at the PM and help maintain membrane integrity. In turn, the growth of ESCRT mutants strongly depended on TORC2-mediated homeostatic regulation of sphingolipid (SL) metabolism. This was caused by calcineurin-dependent dephosphorylation of Orm2, a repressor of SL biosynthesis. Calcineurin activity impaired Orm2 export from the endoplasmic reticulum (ER) and thereby hampered its subsequent endosome and Golgi-associated degradation (EGAD). The ensuing accumulation of Orm2 at the ER in ESCRT mutants necessitated TORC2 signaling through its downstream kinase Ypk1, which repressed Orm2 and prevented a detrimental imbalance of SL metabolism. Our findings reveal compensatory cross-talk between the ESCRT machinery, calcineurin/TORC2 signaling, and the EGAD pathway important for the regulation of SL biosynthesis and the maintenance of PM homeostasis. |
| Databáze: | OpenAIRE |
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