title: A molecular switch on an arrestin-like protein relays glucose signaling to transporter endocytosis.
abstract: 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.
authors.affiliation: Institut Jacques Monod, Centre National de la Recherche Scientifique, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Becuwe
authors.forename: Neide
authors.initials: N
authors.lastname: Vieira
authors.forename: David
authors.initials: D
authors.lastname: Lara
authors.forename: Jéssica
authors.initials: J
authors.lastname: Gomes-Rezende
authors.forename: Carina
authors.initials: C
authors.lastname: Soares-Cunha
authors.forename: Margarida
authors.initials: M
authors.lastname: Casal
authors.forename: Rosine
authors.initials: R
authors.lastname: Haguenauer-Tsapis
authors.forename: Olivier
authors.initials: O
authors.lastname: Vincent
authors.forename: Sandra
authors.initials: S
authors.lastname: Paiva
authors.forename: Sébastien
authors.initials: S
authors.lastname: Léon
mesh_terms: D019393:Arrestin; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D019393:Arrestin; D056827:Endosomal Sorting Complexes Required for Transport; C118697:JEN1 protein, S cerevisiae; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; C099318:ROD1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D027981:Symporters; C485192:green fluorescent protein, Aequorea victoria; D049452:Green Fluorescent Proteins; D043743:Ubiquitin-Protein Ligase Complexes; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; C469287:RSP5 protein, S cerevisiae; D005947:Glucose