NBR1 directly promotes the formation of p62 - ubiquitin condensates via its PB1 and UBA domains
Savova, A.; Romanov, J.; Martens, S.
Show abstract
Selective autophagy removes harmful intracellular structures such as ubiquitinated, aggregated proteins ensuring cellular homeostasis. This is achieved by the encapsulation of this cargo material within autophagosomes. The cargo receptor p62/SQSTM1 mediates the phase separation of ubiquitinated proteins into condensates, which subsequently become targets for the autophagy machinery. NBR1, another cargo receptor, is a crucial regulator of condensate formation. The mechanisms of the interplay between p62 and NBR1 are not well understood. Employing a fully reconstituted system we show that two domains of NBR1, the PB1 domain which binds to p62 and the UBA domain which binds to ubiquitin, are required to promote p62-ubiquitin condensate formation. In cells, acute depletion of endogenous NBR1 reduces formation of p62 condensates, a phenotype that can be rescued by re-expression of wild-type NBR1, but not PB1 or UBA domain mutants. Our results provide mechanistic insights into the role of NBR1 in selective autophagy.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A heterodimeric SNX4:SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly 97%
- Acute perturbation of retromer and ESCPE-1 leads to functionally distinct and temporally resolved defects in endosomal cargo sorting. 95%
- Phosphorylation on serine 72 modulates Rab7A palmitoylation and retromer recruitment 95%
Similar papers in this journal
- Rabaptin5 targets autophagy to damaged early endosomes and Salmonella containing vacuoles by interaction with FIP200 and ATG16L1 96%
- UBAP2L-dependent coupling of PLK1 localization and stability during mitosis 95%
- Loss of the lysosomal protein CLN3 modifies the lipid content of the nuclear envelope leading to DNA damage and activation of YAP1 pro-apoptotic signaling 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.