Hyperactive TORC1 sensitizes yeast cells to endoplasmic reticulum stress by compromising cell wall integrity

FEBS Letters

article

Khadija Ahmed¹  David E. Carter²  Patrick Lajoie¹ 

[1] Department of Anatomy and Cell Biology, The University of Western Ontario;Robarts Research Institute, The University of Western Ontario

关键词: caspofungin;    cell wall integrity;    endoplasmic reticulum stress;    TORC1;    unfolded protein response;   

DOI  :  10.1002/1873-3468.13463

来源: John Wiley & Sons Ltd.

【 摘 要 】

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR). Here, we investigated how the target of rapamycin complex 1 (TORC1) signaling cascade acts in parallel with the UPR to regulate ER stress sensitivity. Using Saccharomyces cerevisiae, we found that TORC1 signaling is attenuated during ER stress and constitutive activation of TORC1 increases sensitivity to ER stressors independently of the UPR. Transcriptome analysis revealed that TORC1 hyperactivation results in cell wall remodelling. Conversely, hyperactive TORC1 sensitizes cells to cell wall stressors, including the antifungal caspofungin. Elucidating the crosstalk between the UPR, cell wall integrity, and TORC1 signaling may uncover new paradigms through which the response to protein misfolding is regulated.

【 授权许可】

Unknown