Ubc13-Mms2 cooperates with a family of RING E3 proteins in budding yeast membrane protein sorting

J Cell Sci. 2020 May 27;133(10):jcs244566. doi: 10.1242/jcs.244566.

Abstract

Polyubiquitin chains linked via lysine (K) 63 play an important role in endocytosis and membrane trafficking. Their primary source is the ubiquitin protein ligase (E3) Rsp5/NEDD4, which acts as a key regulator of membrane protein sorting. The heterodimeric ubiquitin-conjugating enzyme (E2), Ubc13-Mms2, catalyses K63-specific polyubiquitylation in genome maintenance and inflammatory signalling. In budding yeast, the only E3 proteins known to cooperate with Ubc13-Mms2 so far is a nuclear RING finger protein, Rad5, involved in the replication of damaged DNA. Here, we report a contribution of Ubc13-Mms2 to the sorting of membrane proteins to the yeast vacuole via the multivesicular body (MVB) pathway. In this context, Ubc13-Mms2 cooperates with Pib1, a FYVE-RING finger protein associated with internal membranes. Moreover, we identified a family of membrane-associated FYVE-(type)-RING finger proteins as cognate E3 proteins for Ubc13-Mms2 in several species, and genetic analysis indicates that the contribution of Ubc13-Mms2 to membrane trafficking in budding yeast goes beyond its cooperation with Pib1. Thus, our results widely implicate Ubc13-Mms2 as an Rsp5-independent source of K63-linked polyubiquitin chains in the regulation of membrane protein sorting.This article has an associated First Person interview with the first author of the paper.

Keywords: FYVE domain; K63-polyubiquitylation; Membrane protein sorting; RING finger; Ubiquitin protein ligase; Ubiquitin-conjugating enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Membrane Proteins / genetics
  • Polyubiquitin
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomycetales*
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Protein Ligases / genetics

Substances

  • MMS2 protein, S cerevisiae
  • Membrane Proteins
  • Saccharomyces cerevisiae Proteins
  • Polyubiquitin
  • UBC13 protein, S cerevisiae
  • UBE2N protein, human
  • UBE2V2 protein, human
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligases