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Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation

Author

Listed:
  • Eleonora Turco

    (Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC))

  • Adriana Savova

    (Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC))

  • Flora Gere

    (Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC))

  • Luca Ferrari

    (Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC))

  • Julia Romanov

    (Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC))

  • Martina Schuschnig

    (Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC))

  • Sascha Martens

    (Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC))

Abstract

The autophagic degradation of misfolded and ubiquitinated proteins is important for cellular homeostasis. In this process, which is governed by cargo receptors, ubiquitinated proteins are condensed into larger structures and subsequently become targets for the autophagy machinery. Here we employ in vitro reconstitution and cell biology to define the roles of the human cargo receptors p62/SQSTM1, NBR1 and TAX1BP1 in the selective autophagy of ubiquitinated substrates. We show that p62 is the major driver of ubiquitin condensate formation. NBR1 promotes condensate formation by equipping the p62-NBR1 heterooligomeric complex with a high-affinity UBA domain. Additionally, NBR1 recruits TAX1BP1 to the ubiquitin condensates formed by p62. While all three receptors interact with FIP200, TAX1BP1 is the main driver of FIP200 recruitment and thus the autophagic degradation of p62–ubiquitin condensates. In summary, our study defines the roles of all three receptors in the selective autophagy of ubiquitin condensates.

Suggested Citation

  • Eleonora Turco & Adriana Savova & Flora Gere & Luca Ferrari & Julia Romanov & Martina Schuschnig & Sascha Martens, 2021. "Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25572-w
    DOI: 10.1038/s41467-021-25572-w
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    Cited by:

    1. Xuezhao Feng & Daxiao Sun & Yanchang Li & Jinpei Zhang & Shiyu Liu & Dachuan Zhang & Jingxiang Zheng & Qing Xi & Haisha Liang & Wenkang Zhao & Ying Li & Mengbo Xu & Jiayu He & Tong Liu & Ayshamgul Has, 2023. "Local membrane source gathering by p62 body drives autophagosome formation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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