The C-terminal region of the yeast monocarboxylate transporter Jen1 acts as a glucose signal-responding degron recognized by the α-arrestin Rod1.

Shoki Fujita, Daichi Sato, Hirokazu Kasai, Masataka Ohashi, Shintaro Tsukue, Yutaro Takekoshi, Katsuya Gomi, Takahiro Shintani

The Journal of biological chemistry 2018 Jul 13

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In response to changes in nutrient conditions, cells rearrange the composition of plasma membrane (PM) transporters to optimize their metabolic flux. Not only transcriptional gene regulation, but also inactivation of specific transporters is important for fast rearrangement of the PM. In eukaryotic cells, endocytosis plays a role in transporter inactivation, which is triggered by ubiquitination of these transporters. The Nedd4 family E3 ubiquitin ligase is responsible for ubiquitination of the PM transporters and requires that a series of α-arrestin proteins are targeted to these transporters. The mechanism by which an α-arrestin recognizes its cognate transporters in response to environmental signals is of intense scientific interest. Excess substrates or signal transduction pathways are known to initiate recognition of transporters by α-arrestins. Here, we identified an endocytic-sorting signal in the monocarboxylate transporter Jen1 from yeast (Saccharomyces cerevisiae), whose endocytic degradation depends on the Snf1-glucose signaling pathway. We found that the C-terminal 20-amino acid-long region of Jen1 contains an amino acid sequence required for association of Jen1 to the α-arrestin Rod1, as well as lysine residues important for glucose-induced Jen1 ubiquitination. Notably, fusion of this region to the methionine permease, Mup1, whose endocytosis is normally induced by excess methionine, was sufficient for Mup1 to undergo glucose-induced, Rod1-mediated endocytosis. Taken together, our results demonstrate that the Jen1 C-terminal region acts as a glucose-responding degron for α-arrestin-mediated endocytic degradation of Jen1. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Citation

Shoki Fujita, Daichi Sato, Hirokazu Kasai, Masataka Ohashi, Shintaro Tsukue, Yutaro Takekoshi, Katsuya Gomi, Takahiro Shintani. The C-terminal region of the yeast monocarboxylate transporter Jen1 acts as a glucose signal-responding degron recognized by the α-arrestin Rod1. The Journal of biological chemistry. 2018 Jul 13;293(28):10926-10936