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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arrestin
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Endocytosis*
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Endosomal Sorting Complexes Required for Transport / genetics
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Endosomal Sorting Complexes Required for Transport / metabolism
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Glucose / metabolism*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Monocarboxylic Acid Transporters / genetics
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Monocarboxylic Acid Transporters / metabolism
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Protein Processing, Post-Translational
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Signal Transduction*
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Symporters / genetics
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Symporters / metabolism
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Ubiquitin-Protein Ligase Complexes / genetics
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Ubiquitin-Protein Ligase Complexes / metabolism
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Ubiquitination
Substances
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Arrestin
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Endosomal Sorting Complexes Required for Transport
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JEN1 protein, S cerevisiae
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Membrane Proteins
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Membrane Transport Proteins
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Monocarboxylic Acid Transporters
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ROD1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Symporters
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green fluorescent protein, Aequorea victoria
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Green Fluorescent Proteins
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Ubiquitin-Protein Ligase Complexes
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SNF1-related protein kinases
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Protein Serine-Threonine Kinases
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RSP5 protein, S cerevisiae
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Glucose