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

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.

Article and author information

Author details

  1. Bettina Wurzer

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  2. Gabriele Zaffagnini

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  3. Dorotea Fracchiolla

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  4. Eleonora Turco

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Christine Abert

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  6. Julia Romanov

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  7. Sascha Martens

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    For correspondence
    sascha.martens@univie.ac.at
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Randy Schekman, Howard Hughes Medical Institute, University of California, Berkeley, United States

Publication history

  1. Received: May 24, 2015
  2. Accepted: September 26, 2015
  3. Accepted Manuscript published: September 28, 2015 (version 1)
  4. Version of Record published: November 30, 2015 (version 2)

Copyright

© 2015, Wurzer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Bettina Wurzer
  2. Gabriele Zaffagnini
  3. Dorotea Fracchiolla
  4. Eleonora Turco
  5. Christine Abert
  6. Julia Romanov
  7. Sascha Martens
(2015)
Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy
eLife 4:e08941.
https://doi.org/10.7554/eLife.08941
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