title: Quality control and substrate-dependent downregulation of the nutrient transporter Fur4.
abstract: Upon exposure to stress conditions, unfolded cell-surface nutrient transporters are rapidly internalized and degraded via the multivesicular body (MVB) pathway. Similarly, high concentrations of nutrients result in the downregulation of the corresponding transporters. Our studies using the yeast transporter Fur4 revealed that substrate-induced downregulation and quality control utilize a common mechanism. This mechanism is based on a conformation-sensing domain, termed LID (loop interaction domain), that regulates site-specific ubiquitination (also known as degron). Conformational alterations in the transporter induced by unfolding or substrate binding are transmitted to the LID, rendering the degron accessible for ubiquitination by Rsp5. As a consequence, the transporter is rapidly degraded. We propose that the LID-degron system is a conserved, chaperone-independent mechanism responsible for conformation-induced downregulation of many cell-surface transporters under physiological and pathological conditions.
authors.affiliation: Department of Biology and Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112-9202, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Keener
authors.forename: Markus
authors.initials: M
authors.lastname: Babst
mesh_terms: D000595:Amino Acid Sequence; D015536:Down-Regulation; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D008969:Molecular Sequence Data; D033704:Nucleotide Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C035528:FUR4 protein, S cerevisiae; D033704:Nucleotide Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; C469287:RSP5 protein, S cerevisiae