
Phosphorylation of the C-terminal serine residues of the α-arrestin Aly3 by the TORC2 pathway inhibits Aly3-mediated ubiquitination and vacuolar transport of the glucose transporter Ght5, thereby ensuring cell-surface localization of Ght5 and enabling cell proliferation under low glucose conditions in fission yeast.


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In fission yeast, Schizosaccharomyces pombe , transcriptional upregulation and cell-surface localization of the hexose transporter, Ght5, are required for cell proliferation in low glucose. As the target of rapamycin complex 2 (TORC2) signaling pathway inhibits α-arrestin Aly3-dependent endocytosis of Ght5, we hypothesized that this endocytosis was inhibited by phosphorylation. To identify phosphorylation sites required for cell proliferation in low glucose, serine and threonine residues of Aly3 and Ght5 reportedly phosphorylated were replaced with alanine. We found that C-terminal serine residues of Aly3, but not Ght5, are necessary for proliferation in low glucose. Expression of Aly3 protein unphosphorylated at the C-terminus led to increased ubiquitination and vacuolar accumulation of Ght5 in low glucose, but reversion of one of the alanine residues to serine reduced ubiquitination and vacuolar accumulation of Ght5. Also, Aly3 physically interacted with the HECT-type ubiquitin ligases Pub1 and Pub3, and these interactions were required for surface localization of Ght5 and proliferation in low glucose. This study reveals mechanisms by which Aly3 is regulated so that fission yeast can adapt to nutritional stress.

### Competing Interest Statement

The authors have declared no competing interest.

Phosphorylation of Aly3 C-terminus impedes aberrant endocytosis of S. pombe hexose transporter Ght5

phosphorylation-of-the-c-terminus-of-the-α-arrestin-aly3-regulates-glucose-transporter-ght5-localization-and-cell-proliferation-in-fission-yeast-under-low-glucose-conditions


Phosphorylation of the C-terminus of the α-Arrestin Aly3 Regulates Glucose Transporter Ght5 Localization and Cell Proliferation in Fission Yeast under Low Glucose Conditions
