p62 filaments capture and present ubiquitinated cargos for autophagy
The removal of misfolded, ubiquitinated proteins is an essential part of the protein quality control. The ubiquitin‐proteasome system (UPS) and autophagy are two interconnected pathways that mediate the degradation of such proteins. During autophagy, ubiquitinated proteins are clustered in a p62‐dep...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| 格式: | Journal article |
| 语言: | English |
| 出版: |
EMBO Press
2018
|
| _version_ | 1826315055385280512 |
|---|---|
| author | Zaffagnini, G Savova, A Danieli, A Romanov, J Tremel, S Ebner, M Peterbauer, T Sztacho, M Trapannone, R Tarafder, AK Sachse, C Martens, S |
| author_facet | Zaffagnini, G Savova, A Danieli, A Romanov, J Tremel, S Ebner, M Peterbauer, T Sztacho, M Trapannone, R Tarafder, AK Sachse, C Martens, S |
| author_sort | Zaffagnini, G |
| collection | OXFORD |
| description | The removal of misfolded, ubiquitinated proteins is an essential part of the protein quality control. The ubiquitin‐proteasome system (UPS) and autophagy are two interconnected pathways that mediate the degradation of such proteins. During autophagy, ubiquitinated proteins are clustered in a p62‐dependent manner and are subsequently engulfed by autophagosomes. However, the nature of the protein substrates targeted for autophagy is unclear. Here, we developed a reconstituted system using purified components and show that p62 and ubiquitinated proteins spontaneously coalesce into larger clusters. Efficient cluster formation requires substrates modified with at least two ubiquitin chains longer than three moieties and is based on p62 filaments cross‐linked by the substrates. The reaction is inhibited by free ubiquitin, K48‐, and K63‐linked ubiquitin chains, as well as by the autophagosomal marker LC3B, suggesting a tight cross talk with general proteostasis and autophagosome formation. Our study provides mechanistic insights on how substrates are channeled into autophagy. |
| first_indexed | 2024-12-09T03:18:58Z |
| format | Journal article |
| id | oxford-uuid:aaebc376-664d-44c8-bafc-cac1ba1fbaf0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:18:58Z |
| publishDate | 2018 |
| publisher | EMBO Press |
| record_format | dspace |
| spelling | oxford-uuid:aaebc376-664d-44c8-bafc-cac1ba1fbaf02024-10-25T20:16:25Zp62 filaments capture and present ubiquitinated cargos for autophagyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aaebc376-664d-44c8-bafc-cac1ba1fbaf0EnglishJisc Publications RouterEMBO Press2018Zaffagnini, GSavova, ADanieli, ARomanov, JTremel, SEbner, MPeterbauer, TSztacho, MTrapannone, RTarafder, AKSachse, CMartens, SThe removal of misfolded, ubiquitinated proteins is an essential part of the protein quality control. The ubiquitin‐proteasome system (UPS) and autophagy are two interconnected pathways that mediate the degradation of such proteins. During autophagy, ubiquitinated proteins are clustered in a p62‐dependent manner and are subsequently engulfed by autophagosomes. However, the nature of the protein substrates targeted for autophagy is unclear. Here, we developed a reconstituted system using purified components and show that p62 and ubiquitinated proteins spontaneously coalesce into larger clusters. Efficient cluster formation requires substrates modified with at least two ubiquitin chains longer than three moieties and is based on p62 filaments cross‐linked by the substrates. The reaction is inhibited by free ubiquitin, K48‐, and K63‐linked ubiquitin chains, as well as by the autophagosomal marker LC3B, suggesting a tight cross talk with general proteostasis and autophagosome formation. Our study provides mechanistic insights on how substrates are channeled into autophagy. |
| spellingShingle | Zaffagnini, G Savova, A Danieli, A Romanov, J Tremel, S Ebner, M Peterbauer, T Sztacho, M Trapannone, R Tarafder, AK Sachse, C Martens, S p62 filaments capture and present ubiquitinated cargos for autophagy |
| title | p62 filaments capture and present ubiquitinated cargos for autophagy |
| title_full | p62 filaments capture and present ubiquitinated cargos for autophagy |
| title_fullStr | p62 filaments capture and present ubiquitinated cargos for autophagy |
| title_full_unstemmed | p62 filaments capture and present ubiquitinated cargos for autophagy |
| title_short | p62 filaments capture and present ubiquitinated cargos for autophagy |
| title_sort | p62 filaments capture and present ubiquitinated cargos for autophagy |
| work_keys_str_mv | AT zaffagninig p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT savovaa p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT danielia p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT romanovj p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT tremels p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT ebnerm p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT peterbauert p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT sztachom p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT trapannoner p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT tarafderak p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT sachsec p62filamentscaptureandpresentubiquitinatedcargosforautophagy AT martenss p62filamentscaptureandpresentubiquitinatedcargosforautophagy |