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Published on: December 15, 2017
RRD1, a component of the TORC1 signalling pathway, affects anaesthetic response in Saccharomyces cerevisiae
Laura K Palmer1, Beverly A Baptiste, John C Fester
1Division of Mathematics and Natural Sciences, Pennsylvania State University Altoona, College, PA 16601, USA. lkp3@psu.edu
Abstract:
The molecular mechanisms of action of volatile anaesthetics remain unknown despite clinical use for over 150 years. While many effects of these agents have been characterized, clear insight into how these effects relate to the physiological state of anaesthesia has not been established. Volatile anaesthetics arrest cell division in Saccharomyces cerevisiae in a manner that parallels the anaesthetic actions of these drugs in mammals. To gain additional insight into the cellular activities of these drugs, we isolated genes that, when present on multi-copy plasmids, render S. cerevisiae resistant to the volatile anaesthetic isoflurane. One of these genes, RRD1, encodes a subunit of the Tap42p-Sit4p-Rrd1p phosphatase complex that functions in the target of rapamycin complex 1 (TORC1) signalling pathway. In addition, we show that mutations in two other genes encoding components of the TORC1 pathway, GLN3 and URE2, also affect yeast anaesthetic response. These findings suggest that TORC1-mediated signalling is involved in cellular response to volatile anaesthetics in S. cerevisiae.
Insights
Volatile anesthetics
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- The molecular mechanisms of volatile anesthetics are unknown despite extensive clinical use.
- Understanding anesthetic action is crucial for improving patient safety and developing new agents.
- Previous research has characterized many effects but lacked insight into the physiological state of anesthesia.
Purpose of the Study:
- To investigate the cellular mechanisms of volatile anesthetic action.
- To identify genes conferring resistance to isoflurane in Saccharomyces cerevisiae.
- To explore the role of the target of rapamycin complex 1 (TORC1) pathway in anesthetic response.
Main Methods:
- Utilized Saccharomyces cerevisiae as a model organism due to its conserved cellular processes.
- Screened for genes conferring resistance to the volatile anesthetic isoflurane using multi-copy plasmids.
- Investigated the function of identified genes, including RRD1, GLN3, and URE2, within the TORC1 signaling pathway.
Main Results:
- Identified RRD1, encoding a subunit of the Tap42p-Sit4p-Rrd1p phosphatase complex, as conferring isoflurane resistance.
- Demonstrated that RRD1 functions within the target of rapamycin complex 1 (TORC1) signaling pathway.
- Showed that mutations in TORC1 pathway genes GLN3 and URE2 also impact yeast response to anesthetics.
Conclusions:
- The target of rapamycin complex 1 (TORC1) signaling pathway is implicated in the cellular response to volatile anesthetics.
- Findings provide novel insights into the molecular underpinnings of anesthesia.
- Suggests potential therapeutic targets for modulating anesthetic effects.
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