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

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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.

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Bettina Wurzer

Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

Competing interests
The authors declare that no competing interests exist.
Gabriele Zaffagnini

Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

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The authors declare that no competing interests exist.
Dorotea Fracchiolla

Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

Competing interests
The authors declare that no competing interests exist.
Eleonora Turco

Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

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The authors declare that no competing interests exist.
Christine Abert

Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

Competing interests
The authors declare that no competing interests exist.
Julia Romanov

Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

Competing interests
The authors declare that no competing interests exist.
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.

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