Multilevel regulation of an α-arrestin by glucose depletion controls hexose transporter endocytosis.

Nutrient availability controls the landscape of nutrient transporters present at the plasma membrane, notably by regulating their ubiquitylation and subsequent endocytosis. In yeast, this involves the Nedd4 ubiquitin ligase Rsp5 and arrestin-related trafficking adaptors (ARTs). ARTs are targeted by signaling pathways and warrant that cargo ubiquitylation and endocytosis appropriately respond ...
to nutritional inputs. Here, we show that glucose deprivation regulates the ART protein Csr2/Art8 at multiple levels to trigger high-affinity glucose transporter endocytosis. Csr2 is transcriptionally induced in these conditions through the AMPK orthologue Snf1 and downstream transcriptional repressors. Upon synthesis, Csr2 becomes activated by ubiquitylation. In contrast, glucose replenishment induces CSR2 transcriptional shutdown and switches Csr2 to an inactive, deubiquitylated form. This glucose-induced deubiquitylation of Csr2 correlates with its phospho-dependent association with 14-3-3 proteins and involves protein kinase A. Thus, two glucose signaling pathways converge onto Csr2 to regulate hexose transporter endocytosis by glucose availability. These data illustrate novel mechanisms by which nutrients modulate ART activity and endocytosis.
Mesh Terms:
14-3-3 Proteins, Arrestin, Cyclic AMP-Dependent Protein Kinases, Endocytosis, Gene Expression Regulation, Fungal, Glucose, Monosaccharide Transport Proteins, Mutation, Nuclear Proteins, Protein Phosphatase 1, Protein-Serine-Threonine Kinases, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Time Factors, Transcription, Genetic, Ubiquitination
J. Cell Biol.
Date: Jun. 05, 2017
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