Isoflurane induces Art2-Rsp5-dependent endocytosis of Bap2 in yeast

Fumi Kozu; Kanae Shirahama-Noda; Yasuhiro Araki; Shintaro Kira; Hitoshi Niwa; Takeshi Noda

doi:10.1002/2211-5463.13302

Isoflurane induces Art2-Rsp5-dependent endocytosis of Bap2 in yeast

FEBS Open Bio. 2021 Nov;11(11):3090-3100. doi: 10.1002/2211-5463.13302. Epub 2021 Sep 29.

Authors

Fumi Kozu^{1

2}, Kanae Shirahama-Noda¹, Yasuhiro Araki¹, Shintaro Kira¹, Hitoshi Niwa², Takeshi Noda¹

Affiliations

¹ Center of Frontier Oral Science, Graduate School of Dentistry, Osaka University, Suita, Japan.
² Department of dental anesthesiology, 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.

Keywords: anesthetic; arrestin; endocytosis; transporter; ubiquitin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Transport Systems / metabolism
Amino Acid Transport Systems / physiology
Cell Membrane / metabolism
Endocytosis / drug effects
Endocytosis / physiology*
Endosomal Sorting Complexes Required for Transport / genetics
Endosomal Sorting Complexes Required for Transport / metabolism
Isoflurane / metabolism
Isoflurane / pharmacology*
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Saccharomyces cerevisiae Proteins / physiology
Ubiquitin / metabolism
Ubiquitin-Protein Ligase Complexes / genetics
Ubiquitin-Protein Ligase Complexes / metabolism
Ubiquitin-Protein Ligases / metabolism
Ubiquitination

Substances

Amino Acid Transport Systems
BAP2 protein, S cerevisiae
Endosomal Sorting Complexes Required for Transport
Saccharomyces cerevisiae Proteins
Ubiquitin
Isoflurane
Ubiquitin-Protein Ligase Complexes
Ubiquitin-Protein Ligases
RSP5 protein, S cerevisiae