Transient sequestration of TORC1 into stress granules during heat stress

Mol Cell. 2012 Jul 27;47(2):242-52. doi: 10.1016/j.molcel.2012.05.019. Epub 2012 Jun 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytoplasm / metabolism
  • Cytoplasmic Granules / genetics
  • DNA Damage
  • Gene Expression Regulation, Fungal
  • Hot Temperature
  • Microscopy, Fluorescence / methods
  • Models, Genetic
  • Mutation
  • 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*

Substances

  • Saccharomyces cerevisiae Proteins
  • TORC1 protein complex, S cerevisiae
  • Transcription Factors
  • Sirolimus