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.
| Original language | English |
|---|---|
| Pages (from-to) | 796-810 |
| Number of pages | 15 |
| Journal | Molecular Cell |
| Volume | 63 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sep 1 2016 |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
A Surveillance Function of the HSPB8-BAG3-HSP70 Chaperone Complex Ensures Stress Granule Integrity and Dynamism. / Ganassi, Massimo; Mateju, Daniel; Bigi, Ilaria; Mediani, Laura; Poser, Ina; Lee, Hyun O.; Seguin, Samuel J.; Morelli, Federica F.; Vinet, Jonathan; Leo, Giuseppina; Pansarasa, Orietta; Cereda, Cristina; Poletti, Angelo; Alberti, Simon; Carra, Serena.
In: Molecular Cell, Vol. 63, No. 5, 01.09.2016, p. 796-810.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A Surveillance Function of the HSPB8-BAG3-HSP70 Chaperone Complex Ensures Stress Granule Integrity and Dynamism
AU - Ganassi, Massimo
AU - Mateju, Daniel
AU - Bigi, Ilaria
AU - Mediani, Laura
AU - Poser, Ina
AU - Lee, Hyun O.
AU - Seguin, Samuel J.
AU - Morelli, Federica F.
AU - Vinet, Jonathan
AU - Leo, Giuseppina
AU - Pansarasa, Orietta
AU - Cereda, Cristina
AU - Poletti, Angelo
AU - Alberti, Simon
AU - Carra, Serena
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84992445144&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992445144&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2016.07.021
DO - 10.1016/j.molcel.2016.07.021
M3 - Article
AN - SCOPUS:84992445144
VL - 63
SP - 796
EP - 810
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 5
ER -