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A dual role for K63-linked ubiquitin chains in multivesicular body biogenesis and cargo sorting

Erpapazoglou, Z., Dhaoui, M., Pantazopoulou, M., Giordano, F., Mari, M., Léon, S., Raposo, G., Reggiori, F. & Haguenauer-Tsapis, R., Jun-2012, In : Molecular Biology of the Cell. 23, 11, p. 2170-83 14 p.

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DOI

  • Zoi Erpapazoglou
  • Manel Dhaoui
  • Marina Pantazopoulou
  • Francesca Giordano
  • Muriel Mari
  • Sébastien Léon
  • Graça Raposo
  • Fulvio Reggiori
  • Rosine Haguenauer-Tsapis

In yeast, the sorting of transmembrane proteins into the multivesicular body (MVB) internal vesicles requires their ubiquitylation by the ubiquitin ligase Rsp5. This allows their recognition by the ubiquitin-binding domains (UBDs) of several endosomal sorting complex required for transport (ESCRT) subunits. K63-linked ubiquitin (K63Ub) chains decorate several MVB cargoes, and accordingly we show that they localize prominently to the class E compartment, which accumulates ubiquitylated cargoes in cells lacking ESCRT components. Conversely, yeast cells unable to generate K63Ub chains displayed MVB sorting defects. These properties are conserved among eukaryotes, as the mammalian melanosomal MVB cargo MART-1 is modified by K63Ub chains and partly missorted when the genesis of these chains is inhibited. We show that all yeast UBD-containing ESCRT proteins undergo ubiquitylation and deubiquitylation, some being modified through the opposing activities of Rsp5 and the ubiquitin isopeptidase Ubp2, which are known to assemble and disassemble preferentially K63Ub chains, respectively. A failure to generate K63Ub chains in yeast leads to an MVB ultrastructure alteration. Our work thus unravels a double function of K63Ub chains in cargo sorting and MVB biogenesis.

Original languageEnglish
Pages (from-to)2170-83
Number of pages14
JournalMolecular Biology of the Cell
Volume23
Issue number11
Publication statusPublished - Jun-2012
Externally publishedYes

    Keywords

  • Cell Compartmentation, Endosomal Sorting Complexes Required for Transport, Endosomes, HeLa Cells, Humans, Lysine, MART-1 Antigen, Multivesicular Bodies, Protein Structure, Tertiary, Protein Transport, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin, Ubiquitination, YEAST SACCHAROMYCES-CEREVISIAE, RECEPTOR DOWN-REGULATION, AMINO-ACID PERMEASES, DEUBIQUITINATING ENZYME, MEMBRANE-PROTEINS, LIGASE RSP5P, INTRACELLULAR TRAFFICKING, CRYOSECTIONING PROCEDURE, ULTRASTRUCTURAL ANALYSIS, DEPENDENT TRAFFICKING

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