RRD1, a component of the TORC1 signalling pathway, affects anaesthetic response in Saccharomyces cerevisiae.
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.
Palmer
Laura K
LK
Division of Mathematics and Natural Sciences, Pennsylvania State University Altoona, College, PA 16601, USA. lkp3@psu.edu
Baptiste
Beverly A
BA
Fester
John C
JC
Perkins
Justin C
JC
Keil
Ralph L
RL
D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D001483:Base Sequence; D004271:DNA, Fungal / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000235:genetics; D015870:Gene Expression; D005800:Genes, Fungal; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007530:Isoflurane / Q000494:pharmacology; D009154:Mutation; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011328:Prions / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D026905:Amino Acid Transport Systems; D018685:Anesthetics, Inhalation; D004271:DNA, Fungal; C071664:GLN3 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; C470089:TAT1 protein, S cerevisiae; D014157:Transcription Factors; D007530:Isoflurane; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae; D019696:Peptidylprolyl Isomerase; C490203:RRD1 protein, S cerevisiae