A molecular switch on an arrestin-like protein relays glucose signaling to transporter endocytosis

• Autor(a) principal: Becuwe, Michel
• Data de Publicação: 2012
• Outros Autores: Vieira, Neide, Lara, David, Gomes-Rezende, Jéssica, Soares-Cunha, Carina, Casal, Margarida, Haguenauer-Tsapis, Rosine, Vincent, Olivier, Paiva, Sandra, Léon, Sébastien
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/62846
• topic: Arrestin; Endosomal Sorting Complexes Required for Transport; Glucose; Green Fluorescent Proteins; Membrane Proteins; Membrane Transport Proteins; Monocarboxylic Acid Transporters; Protein Processing, Post-Translational; Protein-Serine-Threonine Kinases; Saccharomyces cerevisiae Proteins; Symporters; Ubiquitin-Protein Ligase Complexes; Ubiquitination; Endocytosis; Signal Transduction; Science & Technology

Endocytosis regulates the plasma membrane protein landscape in response to environmental cues. In yeast, the endocytosis of transporters depends on their ubiquitylation by the Nedd4-like ubiquitin ligase Rsp5, but how extracellular signals trigger this ubiquitylation is unknown. Various carbon source transporters are known to be ubiquitylated and endocytosed when glucose-starved cells are exposed to glucose. We show that this required the conserved arrestin-related protein Rod1/Art4, which was activated in response to glucose addition. Indeed, Rod1 was a direct target of the glucose signaling pathway composed of the AMPK homologue Snf1 and the PP1 phosphatase Glc7/Reg1. Glucose promoted Rod1 dephosphorylation and its subsequent release from a phospho-dependent interaction with 14-3-3 proteins. Consequently, this allowed Rod1 ubiquitylation by Rsp5, which was a prerequisite for transporter endocytosis. This paper therefore demonstrates that the arrestin-related protein Rod1 relays glucose signaling to transporter endocytosis and provides the first molecular insights into the nutrient-induced activation of an arrestin-related protein through a switch in post-translational modifications.