| Title: |
NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62 |
| Authors: |
Furthmann, Nikolas; Bader, Verian; van Well, Eva M.; Jaugstetter, Maximilian; Tschulik, Kristina; Damgaard, Rune Busk; Saft, Carsten; Ellrichmann, Gisa; Gold, Ralf; Koch, Arend; Englert, Benjamin; Westenberger, Ana; Angersbach, Lena; Klein, Christine; Jungbluth, Lisa; Sachse, Carsten; Behrends, Christian; Glatzel, Markus; Hartl, F. Ulrich; Nakamura, Ken; Christine, Chadwick W.; Huang, Eric J.; Tatzelt, Jörg; Blusch, Alina; Winklhofer, Konstanze F.; Goel, Simran; Sánchez-Vicente, Ana; Krause, Laura J.; Chaban, Sarah A.; Grover, Prerna; Trinkaus, Victoria A. |
| Source: |
Nature Communications 14(1), 8368 (2023). doi:10.1038/s41467-023-44033-0 |
| Publisher Information: |
Nature Publishing Group UK |
| Publication Year: |
2023 |
| Collection: |
Forschungszentrum Jülich: JuSER (Juelich Shared Electronic Resources) |
| Subject Terms: |
info:eu-repo/classification/ddc/500 |
| Subject Geographic: |
DE |
| Description: |
NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathwayactivation in innate immune signaling, cell death regulation and host-pathogeninteractions. Here we identify an NF-κB-independent function of NEMO inproteostasis regulation by promoting autophagosomal clearance of proteinaggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxicstress and are vulnerable to proteostasis challenges. Moreover, apatient with a mutation in the NEMO-encoding IKBKG gene resulting indefective binding of NEMO to linear ubiquitin chains, developed a widespreadmixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology.NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotesthe local concentration of p62 into foci. In vitro, NEMO lowers the thresholdconcentrations required for ubiquitin-dependent phase transition of p62. Insummary, NEMO reshapes the aggregate surface for efficient autophagosomalclearancebyprovidingamobilephase at theaggregate interphase favoringcocondensationwith p62. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
info:eu-repo/semantics/altIdentifier/issn/2041-1723; info:eu-repo/semantics/altIdentifier/wos/WOS:001131904500002; info:eu-repo/semantics/altIdentifier/pmid/38114471 |
| Availability: |
https://juser.fz-juelich.de/record/1020576; https://juser.fz-juelich.de/search?p=id:%22FZJ-2024-00271%22 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.585C83D4 |
| Database: |
BASE |