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.
journal_name
Autophagyjournal_title
Autophagyauthors
Turco E,Witt M,Abert C,Bock-Bierbaum T,Su MY,Trapannone R,Sztacho M,Danieli A,Shi X,Zaffagnini G,Gamper A,Schuschnig M,Fracchiolla D,Bernklau D,Romanov J,Hartl M,Hurley JH,Daumke O,Martens Sdoi
10.1080/15548627.2019.1615306subject
Has Abstractpub_date
2019-08-01 00:00:00pages
1475-1477issue
8eissn
1554-8627issn
1554-8635journal_volume
15pub_type
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