Abstracts
Short talk 5: TBK1 Induces the Formation of Optineurin Filaments that Condensate with Polyubiquitin and LC3 for Cargo Sequestration
Maria Georgina Herrera
Ruhr Univeristy of Bochum, Medicine, Universitätsstraße 150, 44801 Bochum [DE], maria.herrera@rub.de
Author(s):
Maria Georgina Herrera, Lena Kühn, Lisa Jungbluth, Verian Bader, Laura Krause, David Kartte, Elias Adriaenssens, Sascha Martens, Jörg Tatzelt, Carsten Sachse, Konstanze Winklhofer
Optineurin is an autophagy receptor which plays an important role in the selective degradation of mitochondria, protein aggregates, and intracellular pathogens. It recognizes ubiquitylated cargo by its UBAN (ubiquitin-binding in ABIN and NEMO) domain and recruits the autophagic machinery through its LIR (LC3-interacting region) domain. Phosphorylation of Optineurin by TBK1 (Tank-binding kinase 1) increases the binding of Optineurin to both ubiquitin chains and LC3. Optineurin has been reported to form foci at ubiquitylated cargo, but the underlying mechanism and how these foci are linked to selective autophagy has remained largely unknown. This study shows that the phosphorylation of Optineurin by TBK1 induces the formation of filaments that phase separate upon binding to linear polyubiquitin. LC3 anchored to unilamellar vesicles co-partitions into Optineurin/polyubiquitin condensates, resulting in the local deformation of the vesicle membrane. These data suggest that the condensation of filamentous Optineurin with ubiquitylated cargo promotes the nucleation of cargo and its subsequent alignment with LC3-positive nascent autophagosomes.