TY  - JOUR
AU  - Furthmann, Nikolas
AU  - Bader, Verian
AU  - Angersbach, Lena
AU  - Blusch, Alina
AU  - Goel, Simran
AU  - Sánchez-Vicente, Ana
AU  - Krause, Laura J.
AU  - Chaban, Sarah A.
AU  - Grover, Prerna
AU  - Trinkaus, Victoria A.
AU  - van Well, Eva M.
AU  - Jaugstetter, Maximilian
AU  - Tschulik, Kristina
AU  - Damgaard, Rune Busk
AU  - Saft, Carsten
AU  - Ellrichmann, Gisa
AU  - Gold, Ralf
AU  - Koch, Arend
AU  - Englert, Benjamin
AU  - Westenberger, Ana
AU  - Klein, Christine
AU  - Jungbluth, Lisa
AU  - Sachse, Carsten
AU  - Behrends, Christian
AU  - Glatzel, Markus
AU  - Hartl, F. Ulrich
AU  - Nakamura, Ken
AU  - Christine, Chadwick W.
AU  - Huang, Eric J.
AU  - Tatzelt, Jörg
AU  - Winklhofer, Konstanze F.
TI  - NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - FZJ-2024-00271
SP  - 8368
PY  - 2023
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 38114471
UR  - <Go to ISI:>//WOS:001131904500002
DO  - DOI:10.1038/s41467-023-44033-0
UR  - https://juser.fz-juelich.de/record/1020576
ER  -