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

0477195 - MBÚ 2018 RIV US eng J - Journal Article
Hovsepian, J. - Defenouillere, Q. - Albanese, V. - Váchová, Libuše - Garcia, C. - Palková, Zdena - Léon, S.
Multilevel regulation of an alpha-arrestin by glucose depletion controls hexose transporter endocytosis.
Journal of Cell Biology. Roč. 216, č. 6 (2017), s. 1811-1831. ISSN 0021-9525. E-ISSN 1540-8140
R&D Projects: GA MŠMT(CZ) LQ1604; GA ČR(CZ) GA15-08225S
Institutional support: RVO:61388971
Keywords : YEAST SACCHAROMYCES-CEREVISIAE * BIMOLECULAR FLUORESCENCE COMPLEMENTATION * GAP1 PERMEASE UBIQUITYLATION
OECD category: Microbiology
Impact factor: 8.784, year: 2017

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.
Permanent Link: http://hdl.handle.net/11104/0273568