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Published on: September 17, 2016
Isoflurane induces Art2-Rsp5-dependent endocytosis of Bap2 in yeast
Fumi Kozu1,2, Kanae Shirahama-Noda1, Yasuhiro Araki1
1Center of Frontier Oral Science, Graduate School of Dentistry, Osaka University, Suita, Japan.
Abstract:
Although general anesthesia is indispensable during modern surgical procedures, the mechanism by which inhalation anesthetics act on the synaptic membrane at the molecular and cellular level is largely unknown. In this study, we used yeast cells to examine the effect of isoflurane, an inhalation anesthetic, on membrane proteins. Bap2, an amino acid transporter localized on the plasma membrane, was endocytosed when yeast cells were treated with isoflurane. Depletion of RSP5, an E3 ligase, prevented this endocytosis and Bap2 was ubiquitinated in response to isoflurane, indicating an ubiquitin-dependent process. Screening all the Rsp5 binding adaptors showed that Art2 plays a central role in this process. These results suggest that isoflurane affects Bap2 via an Art2-Rsp5-dependent ubiquitination system.
Insights
Inhalation anesthetics like isoflurane trigger the endocytosis of the amino acid transporter Bap2 in yeast cells. This process is dependent on ubiquitination, involving the Art2-Rsp5 system.
Area of Science:
- Cell Biology
- Molecular Pharmacology
- Anesthesiology
Background:
- General anesthesia is crucial for surgery, but its molecular mechanisms remain unclear.
- Inhalation anesthetics interact with synaptic membranes, yet their cellular targets are largely unknown.
Purpose of the Study:
- To investigate the molecular effects of the inhalation anesthetic isoflurane on membrane proteins.
- To elucidate the cellular pathway involved in isoflurane's action on yeast plasma membrane proteins.
Main Methods:
- Utilized yeast cells as a model system to study isoflurane's impact on membrane proteins.
- Investigated the endocytosis of the amino acid transporter Bap2 upon isoflurane treatment.
- Examined the role of ubiquitination and specific proteins (RSP5, Art2) in the observed cellular response.
Main Results:
- Isoflurane induced the endocytosis of Bap2, an amino acid transporter, in yeast cells.
- Depletion of the E3 ligase RSP5 inhibited isoflurane-induced Bap2 endocytosis.
- Bap2 ubiquitination was observed in response to isoflurane, confirming an ubiquitin-dependent pathway.
- Art2 was identified as a key adaptor protein in the Art2-Rsp5-dependent ubiquitination system.
Conclusions:
- Isoflurane perturbs membrane protein trafficking via an ubiquitin-dependent mechanism.
- The Art2-Rsp5 ubiquitination system mediates the effect of isoflurane on the Bap2 amino acid transporter.
- This study provides molecular insights into the action of inhalation anesthetics at the cellular level.
