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How RB1CC1/FIP200 claws its way to autophagic engulfment of SQSTM1/p62-ubiquitin condensates

Item Type:Editorial
Title:How RB1CC1/FIP200 claws its way to autophagic engulfment of SQSTM1/p62-ubiquitin condensates
Creators Name:Turco, E. and Witt, M. and Abert, C. and Bock-Bierbaum, T. and Su, M.Y. and Trapannone, R. and Sztacho, M. and Danieli, A. and Shi, X. and Zaffagnini, G. and Gamper, A. and Schuschnig, M. and Fracchiolla, D. and Bernklau, D. and Romanov, J. and Hartl, M. and Hurley, J.H. and Daumke, O. and Martens, S.
Abstract:Macroautophagy/autophagy mediates the degradation of ubiquitinated aggregated proteins within lysosomes in a process known as aggrephagy. The cargo receptor SQSTM1/p62 condenses aggregated proteins into larger structures and links them to the nascent autophagosomal membrane (phagophore). How the condensation reaction and autophagosome formation are coupled is unclear. We recently discovered that a region of SQSTM1 containing its LIR motif directly interacts with RB1CC1/FIP200, a protein acting at early stages of autophagosome formation. Determination of the structure of the C-terminal region of RB1CC1 revealed a claw-shaped domain. Using a structure-function approach, we show that the interaction of SQSTM1 with the RB1CC1 claw domain is crucial for the productive recruitment of the autophagy machinery to ubiquitin-positive condensates and their subsequent degradation by autophagy. We also found that concentrated Atg8-family proteins on the phagophore displace RB1CC1 from SQSTM1, suggesting an intrinsic directionality in the process of autophagosome formation. Ultimately, our study reveals how the interplay of SQSTM1 and RB1CC1 couples cargo condensation to autophagosome formation.
Keywords:Aggrephagy, Atg8, Autophagosome, Autophagy, Cargo Receptor, Phase Separation, Protein Quality Control, ULK1, Animals
Publisher:Taylor & Francis
Page Range:1475-1477
Date:August 2019
Official Publication:https://doi.org/10.1080/15548627.2019.1615306
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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