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- W3200710526 abstract "Selective endocytosis followed by degradation is a major mechanism for downregulating plasma membrane transporters in response to specific environmental cues. In Saccharomyces cerevisiae, this endocytosis is promoted by ubiquitylation catalyzed by the Rsp5 ubiquitin-ligase, targeted to transporters via adaptors of the alpha-arrestin family. However, the molecular mechanisms of this targeting and their control according to conditions remain incompletely understood. In this work, we dissect the molecular mechanisms eliciting the endocytosis of Can1, the arginine permease, in response to cycloheximide-induced TORC1 hyperactivation. We show that cycloheximide promotes Rsp5-dependent Can1 ubiquitylation and endocytosis in a manner dependent on the Bul1/2 alpha-arrestins. Also crucial for this downregulation is a short acidic patch sequence in the N-terminus of Can1 likely acting as a binding site for Bul1/2. The previously reported inhibition by cycloheximide of transporter recycling, from the trans-Golgi network to the plasma membrane, seems to additionally contribute to efficient Can1 downregulation. Our results also indicate that, contrary to the previously described substrate-transport elicited Can1 endocytosis mediated by the Art1 alpha-arrestin, Bul1/2-mediated Can1 ubiquitylation occurs independently of the conformation of the transporter. This study provides further insights into how distinct alpha-arrestins control the ubiquitin-dependent downregulation of a specific amino acid transporter under different conditions." @default.
- W3200710526 created "2021-09-27" @default.
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- W3200710526 creator A5070626519 @default.
- W3200710526 creator A5083493500 @default.
- W3200710526 date "2021-09-22" @default.
- W3200710526 modified "2023-10-01" @default.
- W3200710526 title "The Bul1/2 Alpha-Arrestins Promote Ubiquitylation and Endocytosis of the Can1 Permease upon Cycloheximide-Induced TORC1-Hyperactivation" @default.
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- W3200710526 doi "https://doi.org/10.3390/ijms221910208" @default.
- W3200710526 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8508209" @default.
- W3200710526 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34638549" @default.
- W3200710526 hasPublicationYear "2021" @default.
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