title: 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.
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wurzer
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.|Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Zaffagnini
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.|Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Dorotea
authors.initials: D
authors.lastname: Fracchiolla
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Turco
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Abert
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Romanov
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.|Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.|Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Sascha
authors.initials: S
authors.lastname: Martens
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001343:Autophagy; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin
keywords: biochemistry; cargo receptor; cell biology; human; in vitro reconstitution; selective autophagy