title: Membrane-anchored ubiquitin ligase complex is required for the turnover of lysosomal membrane proteins.
abstract: Cells must regulate the abundance and activity of numerous nutrient transporters in different organelle membranes to achieve nutrient homeostasis. As the recycling center and major storage organelle, lysosomes are essential for maintaining nutrient homeostasis. However, very little is known about mechanisms that govern the regulation of its membrane proteins. In this study, we demonstrated that changes of Zn(2+) levels trigger the downregulation of vacuolar Zn(2+) transporters. Low Zn(2+) levels cause the degradation of the influx transporter Cot1, whereas high Zn(2+) levels trigger the degradation of the efflux channel Zrt3. The degradation process depends on the vacuole membrane recycling and degradation pathway. Unexpectedly, we identified a RING domain-containing E3 ligase Tul1 and its interacting proteins in the Dsc complex that are important for the ubiquitination of Cot1 and partial ubiquitination of Zrt3. Our study demonstrated that the Dsc complex can function at the vacuole to regulate the composition and lifetime of vacuolar membrane proteins.
authors.affiliation: Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Koshi
authors.affiliation: Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853 sde26@cornell.edu.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Emr
mesh_terms: D015536:Down-Regulation / Q000502:physiology; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008566:Membranes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology; D015032:Zinc / Q000378:metabolism
chemical_list: D051907:Lysosomal Membrane Proteins; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases; D015032:Zinc