A Surveillance Function of the HSPB8-BAG3-HSP70 Chaperone Complex Ensures Stress Granule Integrity and Dynamism

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Massimo Ganassi - , University of Modena and Reggio Emilia (Autor:in)
  • Daniel Mateju - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Ilaria Bigi - , University of Modena and Reggio Emilia (Autor:in)
  • Laura Mediani - , University of Modena and Reggio Emilia (Autor:in)
  • Ina Poser - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Hyun O. Lee - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Samuel J. Seguin - , University of Modena and Reggio Emilia (Autor:in)
  • Federica F. Morelli - , University of Modena and Reggio Emilia (Autor:in)
  • Jonathan Vinet - , University of Modena and Reggio Emilia (Autor:in)
  • Giuseppina Leo - , University of Modena and Reggio Emilia (Autor:in)
  • Orietta Pansarasa - , IRCCS Fondazione Istituto Neurologico Casimiro Mondino - Pavia (Autor:in)
  • Cristina Cereda - , IRCCS Fondazione Istituto Neurologico Casimiro Mondino - Pavia (Autor:in)
  • Angelo Poletti - , University of Milan (Autor:in)
  • Simon Alberti - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Serena Carra - , University of Modena and Reggio Emilia (Autor:in)

Abstract

Stress granules (SGs) are ribonucleoprotein complexes induced by stress. They sequester mRNAs and disassemble when the stress subsides, allowing translation restoration. In amyotrophic lateral sclerosis (ALS), aberrant SGs cannot disassemble and therefore accumulate and are degraded by autophagy. However, the molecular events causing aberrant SG formation and the molecular players regulating this transition are largely unknown. We report that defective ribosomal products (DRiPs) accumulate in SGs and promote a transition into an aberrant state that renders SGs resistant to RNase. We show that only a minor fraction of aberrant SGs is targeted by autophagy, whereas the majority disassembles in a process that requires assistance by the HSPB8-BAG3-HSP70 chaperone complex. We further demonstrate that HSPB8-BAG3-HSP70 ensures the functionality of SGs and restores proteostasis by targeting DRiPs for degradation. We propose a system of chaperone-mediated SG surveillance, or granulostasis, which regulates SG composition and dynamics and thus may play an important role in ALS.

Details

OriginalspracheEnglisch
Seiten (von - bis)796-810
Seitenumfang15
FachzeitschriftMolecular cell
Jahrgang63
Ausgabenummer5
PublikationsstatusVeröffentlicht - 1 Sep. 2016
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

PubMed 27570075

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Bibliotheksschlagworte