Membrane-anchored ubiquitin ligase complex is required for the turnover of lysosomal membrane proteins. Academic Article uri icon

Overview

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.

publication date

  • November 2, 2015

Research

keywords

  • Lysosome-Associated Membrane Glycoproteins
  • Lysosomes
  • Membranes
  • Ubiquitin-Protein Ligases

Identity

PubMed Central ID

  • PMC4639871

Scopus Document Identifier

  • 84980349624

Digital Object Identifier (DOI)

  • 10.1126/science.1207056

PubMed ID

  • 26527740

Additional Document Info

volume

  • 211

issue

  • 3