Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
  Proteomics and C9orf72 neuropathology identify ribosomes as poly-GR/PR interactors driving toxicity

Hartmann, H., Hornburg, D., Czuppa, M., Bader, J. M., Michaelsen, M., Farny, D., et al. (2018). Proteomics and C9orf72 neuropathology identify ribosomes as poly-GR/PR interactors driving toxicity. Life science alliance, 1(2): e201800070. doi:10.26508/lsa.201800070.

Item is

Basisdaten

ausblenden:
Genre: Zeitschriftenartikel

Dateien

ausblenden: Dateien
:
e201800070.full.pdf (Verlagsversion), 3MB
Name:
e201800070.full.pdf
Beschreibung:
-
OA-Status:
Keine Angabe
Sichtbarkeit:
Öffentlich
MIME-Typ / Prüfsumme:
application/pdf / [MD5]
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
© 2018 Hartmann et al.

Externe Referenzen

ausblenden:
externe Referenz:
https://doi.org/10.26508/lsa.201800054 (Ergänzendes Material)
Beschreibung:
-
OA-Status:
Keine Angabe

Urheber

ausblenden:
 Urheber:
Hartmann, Hannelore, Autor
Hornburg, Daniel1, Autor           
Czuppa, Mareike, Autor
Bader, Jakob Maximilian1, Autor           
Michaelsen, Meike, Autor
Farny, Daniel, Autor
Arzberger, Thomas, Autor
Mann, Matthias1, Autor           
Meissner, Felix2, Autor           
Edbauer, Dieter, Autor
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

Inhalt

ausblenden:
Schlagwörter: -
 Zusammenfassung: Frontotemporal dementia and amyotrophic lateral sclerosis patients with C9orf72 mutation show cytoplasmic poly-GR and poly-PR aggregates. Short poly-(Gly-Arg) and poly-(Pro-Arg) (poly-GR/PR) repeats localizing to the nucleolus are toxic in various model systems, but no interactors have been validated in patients. Here, the neuronal interactomes of cytoplasmic GFP-(GR)149 and nucleolar (PR)175-GFP revealed overlapping RNA-binding proteins, including components of stress granules, nucleoli, and ribosomes. Overexpressing the poly-GR/PR interactors STAU1/2 and YBX1 caused cytoplasmic aggregation of poly-GR/PR in large stress granule–like structures, whereas NPM1 recruited poly-GR into the nucleolus. Poly-PR expression reduced ribosome levels and translation consistent with reduction of synaptic proteins detected by proteomics. Surprisingly, truncated GFP-(GR)53, but not GFP-(GR)149, localized to the nucleolus and reduced ribosome levels and translation similar to poly-PR, suggesting that impaired ribosome biogenesis may be driving the acute toxicity observed in vitro. In patients, only ribosomes and STAU2 co-aggregated with poly-GR/PR. Partial sequestration of ribosomes may chronically impair protein synthesis even in the absence of nucleolar localization and contribute to pathogenesis.

Details

ausblenden:
Sprache(n):
 Datum: 2018-05
 Publikationsstatus: Online veröffentlicht
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000457325800008
DOI: 10.26508/lsa.201800070
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

ausblenden:
Projektname : ToPAG
Grant ID : 318987
Förderprogramm : European Community’s Health Seventh Framework Programme
Förderorganisation : European Commission (EC)
Projektname : EUROMOTOR
Grant ID : 259867
Förderprogramm : European Community’s Health Seventh Framework Programme
Förderorganisation : European Commission (EC)

Quelle 1

ausblenden:
Titel: Life science alliance
  Kurztitel : Life Sci Alliance
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: Heidelberg : EMBO Press
Seiten: - Band / Heft: 1 (2) Artikelnummer: e201800070 Start- / Endseite: - Identifikator: ISSN: 2575-1077
CoNE: https://pure.mpg.de/cone/journals/resource/2575-1077