Montenegro-Venegas2021_Article_BassoonInhibitsProteasomeActiv.pdf 2,34MB
1000 Titel
  • Bassoon inhibits proteasome activity via interaction with PSMB4
1000 Autor/in
  1. Montenegro Venegas, Carolina |
  2. Fienko, Sandra |
  3. Anni, Daniela |
  4. Pina‐Fernández, Eneko |
  5. Frischknecht, Renato |
  6. Fejtova, Anna |
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-07-10
1000 Erschienen in
1000 Quellenangabe
  • 78(4):1545-1563
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Ergänzendes Material
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Proteasomes are protein complexes that mediate controlled degradation of damaged or unneeded cellular proteins. In neurons, proteasome regulates synaptic function and its dysfunction has been linked to neurodegeneration and neuronal cell death. However, endogenous mechanisms controlling proteasomal activity are insufficiently understood. Here, we describe a novel interaction between presynaptic scaffolding protein bassoon and PSMB4, a β subunit of the 20S core proteasome. Expression of bassoon fragments that interact with PSMB4 in cell lines or in primary neurons attenuates all endopeptidase activities of cellular proteasome and induces accumulation of several classes of ubiquitinated and non-ubiquitinated substrates of the proteasome. Importantly, these effects are distinct from the previously reported impact of bassoon on ubiquitination and autophagy and might rely on a steric interference with the assembly of the 20S proteasome core. In line with a negative regulatory role of bassoon on endogenous proteasome we found increased proteasomal activity in the synaptic fractions prepared from brains of bassoon knock-out mice. Finally, increased activity of proteasome and lower expression levels of synaptic substrates of proteasome could be largely normalized upon expression of PSMB4-interacting fragments of bassoon in neurons derived from bassoon deficient mice. Collectively, we propose that bassoon interacts directly with proteasome to control its activity at presynapse and thereby it contributes to a compartment-specific regulation of neuronal protein homeostasis. These findings provide a mechanistic explanation for the recently described link of bassoon to human diseases associated with pathological protein aggregation. Presynaptic cytomatrix protein bassoon (Bsn) interacts with PSMB4, the β7 subunit of 20S core proteasome, via three independent interaction interfaces. Bsn inhibits proteasomal proteolytic activity and degradation of different classes of proteasomal substrates presumably due to steric interference with the assembly of 20S core of proteasome. Upon Bsn deletion in neurons, presynaptic substrates of the proteasome are depleted, which can be reversed upon expression of PSMB4-interacting interfaces of Bsn. Taken together, bsn controls the degree of proteasome degradation within the presynaptic compartment and thus, contributes to the regulation of synaptic proteome.
1000 Sacherschließung
lokal Synapse
lokal Proteostasis
lokal Protein degradation
lokal Ubiquitin–proteasome system
lokal Cytomatrix at the active zone
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 Label
1000 Förderer
  1. Projekt DEAL |
  2. Deutsche Forschungsgemeinschaft |
  3. Leibniz-Gemeinschaft |
1000 Fördernummer
  1. -
  2. FE1335/1; FE1335/3; SFB779-A06; 270949263/GRK2162; SFB779-B14
  3. SAW 2014-2016
1000 Förderprogramm
  1. Open Access Funding
  2. -
  3. -
1000 Dateien
  1. Bassoon inhibits proteasome activity via interaction with PSMB4
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Projekt DEAL |
    1000 Förderprogramm Open Access Funding
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer FE1335/1; FE1335/3; SFB779-A06; 270949263/GRK2162; SFB779-B14
  3. 1000 joinedFunding-child
    1000 Förderer Leibniz-Gemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer SAW 2014-2016
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6426276.rdf
1000 Erstellt am 2021-03-19T14:13:19.316+0100
1000 Erstellt von 242
1000 beschreibt frl:6426276
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Fri May 13 16:36:44 CEST 2022
1000 Objekt bearb. Fri May 13 16:36:44 CEST 2022
1000 Vgl. frl:6426276
1000 Oai Id
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1000 Sichtbarkeit Metadaten public
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