2023-07-19 カリフォルニア大学サンタバーバラ校(UCSB)
◆この研究は、ストレスに関連した疾患の発症を解明するだけでなく、予防や治療法の開発にも繋がる可能性があります。光を用いた方法により、細胞の応答を正確に観察できるため、ストレスによる応答をより詳細に理解することが可能です。将来的には、ストレスに関連した疾患のメカニズムを解明し、より効果的な治療法の開発につながるかもしれません。
<関連情報>
- https://www.news.ucsb.edu/2023/021132/first-map-cellular-stress-memory-landscape-paves-way-better-understanding-cell-stress
- https://www.cell.com/cell-systems/fulltext/S2405-4712(23)00154-0
統合ストレス応答の光遺伝学的制御により、比例的エンコードとストレスメモリーランドスケープが明らかになった Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape
Taivan Batjargal,Francesca Zappa,Ryan J. Grant,Robert A. Piscopio,Alex Chialastri,Siddharth S. Dey,Diego Acosta-Alvear,Maxwell Z. Wilson
Cell Systems Published:JULY 19, 2023
DOI:https://doi.org/10.1016/j.cels.2023.06.001
Highlights
•Optogenetic activation of PKR induces a stressless stress response
•The ISR has early and late phases corresponding to adaptive and terminal outcomes
•Key ISR pathway nodes respond proportionally to the intensity of the stress input
•Both the model and experiment map the dependence of future responses on past ISR activations
Summary
The integrated stress response (ISR) is a conserved signaling network that detects aberrations and computes cellular responses. Dissecting these computations has been difficult because physical and chemical inducers of stress activate multiple parallel pathways. To overcome this challenge, we engineered a photo-switchable control over the ISR sensor kinase PKR (opto-PKR), enabling virtual, on-target activation. Using light to control opto-PKR dynamics, we traced information flow through the transcriptome and for key downstream ISR effectors. Our analyses revealed a biphasic, proportional transcriptional response with two dynamic modes, transient and gradual, that correspond to adaptive and terminal outcomes. We then constructed an ordinary differential equation (ODE) model of the ISR, which demonstrated the dependence of future stress responses on past stress. Finally, we tested our model using high-throughput light-delivery to map the stress memory landscape. Our results demonstrate that cells encode information in stress levels, durations, and the timing between encounters.
