Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress
In eukaryotes, exposure to hypertonic conditions activates a MAPK (Hog1 in Saccharomyces cerevisiae and ortholog p38 in human cells). In yeast, intracellular glycerol accumulates to counterbalance the high external osmolarity. To prevent glycerol efflux, Hog1 action impedes the function of the aquag...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/09336 |
| _version_ | 1811236803630333952 |
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| author | Alexander Muir Françoise M Roelants Garrett Timmons Kristin L Leskoske Jeremy Thorner |
| author_facet | Alexander Muir Françoise M Roelants Garrett Timmons Kristin L Leskoske Jeremy Thorner |
| author_sort | Alexander Muir |
| collection | DOAJ |
| description | In eukaryotes, exposure to hypertonic conditions activates a MAPK (Hog1 in Saccharomyces cerevisiae and ortholog p38 in human cells). In yeast, intracellular glycerol accumulates to counterbalance the high external osmolarity. To prevent glycerol efflux, Hog1 action impedes the function of the aquaglyceroporin Fps1, in part, by displacing channel co-activators (Rgc1/2). However, Fps1 closes upon hyperosmotic shock even in hog1∆ cells, indicating another mechanism to prevent Fps1-mediated glycerol efflux. In our prior proteome-wide screen, Fps1 was identified as a target of TORC2-dependent protein kinase Ypk1 (Muir et al., 2014). We show here that Fps1 is an authentic Ypk1 substrate and that the open channel state of Fps1 requires phosphorylation by Ypk1. Moreover, hyperosmotic conditions block TORC2-dependent Ypk1-mediated Fps1 phosphorylation, causing channel closure, glycerol accumulation, and enhanced survival under hyperosmotic stress. These events are all Hog1-independent. Our findings define the underlying molecular basis of a new mechanism for responding to hypertonic conditions. |
| first_indexed | 2024-04-12T12:14:22Z |
| format | Article |
| id | doaj.art-482db70761b04231aedbb002e3f1c59d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:14:22Z |
| publishDate | 2015-08-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-482db70761b04231aedbb002e3f1c59d2022-12-22T03:33:28ZengeLife Sciences Publications LtdeLife2050-084X2015-08-01410.7554/eLife.09336Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stressAlexander Muir0Françoise M Roelants1Garrett Timmons2Kristin L Leskoske3Jeremy Thorner4Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Chemical Biology Graduate Program, University of California, Berkeley, Berkeley, United StatesDivision of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Chemistry, University of California, Berkeley, Berkeley, United StatesDivision of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesIn eukaryotes, exposure to hypertonic conditions activates a MAPK (Hog1 in Saccharomyces cerevisiae and ortholog p38 in human cells). In yeast, intracellular glycerol accumulates to counterbalance the high external osmolarity. To prevent glycerol efflux, Hog1 action impedes the function of the aquaglyceroporin Fps1, in part, by displacing channel co-activators (Rgc1/2). However, Fps1 closes upon hyperosmotic shock even in hog1∆ cells, indicating another mechanism to prevent Fps1-mediated glycerol efflux. In our prior proteome-wide screen, Fps1 was identified as a target of TORC2-dependent protein kinase Ypk1 (Muir et al., 2014). We show here that Fps1 is an authentic Ypk1 substrate and that the open channel state of Fps1 requires phosphorylation by Ypk1. Moreover, hyperosmotic conditions block TORC2-dependent Ypk1-mediated Fps1 phosphorylation, causing channel closure, glycerol accumulation, and enhanced survival under hyperosmotic stress. These events are all Hog1-independent. Our findings define the underlying molecular basis of a new mechanism for responding to hypertonic conditions.https://elifesciences.org/articles/09336aquaglyceroporinprotein kinaseosmosensing |
| spellingShingle | Alexander Muir Françoise M Roelants Garrett Timmons Kristin L Leskoske Jeremy Thorner Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress eLife aquaglyceroporin protein kinase osmosensing |
| title | Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress |
| title_full | Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress |
| title_fullStr | Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress |
| title_full_unstemmed | Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress |
| title_short | Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress |
| title_sort | down regulation of torc2 ypk1 signaling promotes mapk independent survival under hyperosmotic stress |
| topic | aquaglyceroporin protein kinase osmosensing |
| url | https://elifesciences.org/articles/09336 |
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