Nejvíce citovaný článek - PubMed ID 10361302
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
- arrestin genetika metabolismus MeSH
- časové faktory MeSH
- endocytóza * MeSH
- genetická transkripce MeSH
- glukosa nedostatek MeSH
- jaderné proteiny genetika metabolismus MeSH
- mutace MeSH
- protein-serin-threoninkinasy metabolismus MeSH
- proteinfosfatasa 1 metabolismus MeSH
- proteinkinasy závislé na cyklickém AMP metabolismus MeSH
- proteiny 14-3-3 metabolismus MeSH
- proteiny přenášející monosacharidy genetika metabolismus MeSH
- regulace genové exprese u hub MeSH
- represorové proteiny metabolismus MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae genetika metabolismus MeSH
- ubikvitinace MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- arrestin MeSH
- BMH1 protein, S cerevisiae MeSH Prohlížeč
- BMH2 protein, S cerevisiae MeSH Prohlížeč
- Csr2 protein, S cerevisiae MeSH Prohlížeč
- glukosa MeSH
- Hxt6 protein, S cerevisiae MeSH Prohlížeč
- HXT7 protein, S cerevisiae MeSH Prohlížeč
- jaderné proteiny MeSH
- MIG1 protein, S cerevisiae MeSH Prohlížeč
- Mig2 protein, S cerevisiae MeSH Prohlížeč
- protein-serin-threoninkinasy MeSH
- proteinfosfatasa 1 MeSH
- proteinkinasy závislé na cyklickém AMP MeSH
- proteiny 14-3-3 MeSH
- proteiny přenášející monosacharidy MeSH
- represorové proteiny MeSH
- Saccharomyces cerevisiae - proteiny MeSH
- SNF1-related protein kinases MeSH Prohlížeč