Transient Sequestration of TORC1 into Stress Granules during Heat Stress

The target of rapamycin complex 1 (TORC1) is a central kinase that coordinates nutrient availability with eukaryotic cell growth. Although TORC1 signaling is repressed by various stresses in yeast, the underlying mechanisms remain elusive. Here we report that TORC1 signaling upon heat stress is regu...

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Bibliographic Details
Published in:Molecular cell 2012-07, Vol.47 (2), p.242-252
Main Authors: Takahara, Terunao, Maeda, Tatsuya
Format: Article
Language:English
Subjects:
cell growth
Cytoplasm - metabolism
cytoplasmic granules
Cytoplasmic Granules - genetics
DNA Damage
eukaryotic cells
Gene Expression Regulation, Fungal
heat stress
Hot Temperature
Microscopy, Fluorescence - methods
Models, Genetic
Mutation
nutrient availability
Phosphorylation
Protein Biosynthesis
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Signal Transduction
Sirolimus - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
yeasts
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Summary:The target of rapamycin complex 1 (TORC1) is a central kinase that coordinates nutrient availability with eukaryotic cell growth. Although TORC1 signaling is repressed by various stresses in yeast, the underlying mechanisms remain elusive. Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling. Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress. Moreover, TORC1 reactivation is directed through SG disassembly, suggesting that SGs act as a key determinant for TORC1 reactivation during recovery from heat stress. Furthermore, this mechanism contributes to reduction of heat-induced mutations. Thus, TORC1 signaling is coupled to heat-induced SGs to protect cells from DNA damage. ► Stress granules (SGs) induced by Pbp1 overexpression repress TORC1 activation ► TORC1 is sequestered into SGs upon heat stress ► TORC1 reactivation is directed through SG disassembly ► SG-mediated repression of TORC1 functions to suppress heat-induced mutations
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2012.05.019