Proteomic analysis reveals the role of Art2 α-arrestin in endocytosis of the thiamine transporter Thi7 in Saccharomyces cerevisiae
(2018)
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- Authors
- Supervisors
- Morsomme, Pierre
- Abstract
- The plasma membrane (PM) constitutes the first barrier separating the cell from its external medium. The PM protein and lipid composition must be tightly regulated for the adaptation of cells to their surrounding environment, ensuring a good nutritional status and proper responses to environmental cues. One essential mechanism underlying that regulation is endocytosis. In the yeast Saccharomyces cerevisiae, endocytosis of proteins is triggered by their ubiquitylation, which is catalyzed by a single ubiquitin ligase, Rsp5. However, 240 proteins are predicted to be localized at the PM. To ubiquitylate such a high number of targets, Rsp5 interacts with adaptor proteins, the α-arrestins. The α-arrestins bridge Rsp5 and its targets, thereby mediating the ubiquitylation of PM proteins. The genome of S. cerevisiae encodes thirteen adaptors but only a few PM proteins were shown to interact with them so far, leading to an incomplete understanding of their regulation. To broaden our knowledge on α-arrestin involvement, the first part of this study focused on the identification of new targets of the α-arrestin system in an unbiased fashion. To that end, we performed a quantitative proteomic screening that led us to the discovery of 28 potential new targets. Among these, we decided to further investigate a poorly known subset of transporters, thiamine (vitamin B1) transporters. The second part of the study dealt with the characterization of the α-arrestin-mediated endocytosis of thiamine transporters. We unraveled the role of Art2 α-arrestin in the thiamine and stress-induced ubiquitylation and endocytosis of thiamine transporters. Art2 proves to be a new player in thiamine homeostasis by fine-tuning the abundance of thiamine transporters in response to various signals.
- Affiliations
Citations
Savocco, J. (2018). Proteomic analysis reveals the role of Art2 α-arrestin in endocytosis of the thiamine transporter Thi7 in Saccharomyces cerevisiae. https://hdl.handle.net/2078.5/126381