Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy

Elife. 2015 Sep 28;4:e08941. doi: 10.7554/eLife.08941.

Abstract

Autophagy is a major pathway for the clearance of harmful material from the cytoplasm. During autophagy, cytoplasmic material is delivered into the lysosomal system by organelles called autophagosomes. Autophagosomes form in a de novo manner and, in the course of their formation, isolate cargo material from the rest of the cytoplasm. Cargo specificity is conferred by autophagic cargo receptors that selectively link the cargo to the autophagosomal membrane decorated with ATG8 family proteins such as LC3B. Here we show that the human cargo receptor p62/SQSTM-1 employs oligomerization to stabilize its interaction with LC3B and linear ubiquitin when they are clustered on surfaces. Thus, oligomerization enables p62 to simultaneously select for the isolation membrane and the ubiquitinated cargo. We further show in a fully reconstituted system that the interaction of p62 with ubiquitin and LC3B is sufficient to bend the membrane around the cargo.

Keywords: biochemistry; cargo receptor; cell biology; human; in vitro reconstitution; selective autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Autophagy*
  • Humans
  • Intracellular Membranes / metabolism*
  • Microtubule-Associated Proteins / metabolism
  • Protein Binding
  • Protein Multimerization*
  • Sequestosome-1 Protein
  • Ubiquitin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Ubiquitin