Nanoscale Analysis Reveals the Maturation of Neurodegeneration-Associated Protein Aggregates: Grown in mRNA Granules then Released by Stress Granule Proteins

ACS Nano ◽  
2017 ◽  
Vol 11 (7) ◽  
pp. 7189-7200 ◽  
Author(s):  
Sanae Abrakhi ◽  
Dmitry A. Kretov ◽  
Bénédicte Desforges ◽  
Ioana Dobra ◽  
Ahmed Bouhss ◽  
...  
Keyword(s):  
Protein Aggregates ◽  
Stress Granule ◽  
Mrna Granules ◽  
Granule Proteins

scholarly journals Small molecules for modulating protein driven liquid-liquid phase separation in treating neurodegenerative disease

2019 ◽  
Author(s):  
Richard J. Wheeler ◽  
Hyun O. Lee ◽  
Ina Poser ◽  
Arun Pal ◽  
Thom Doeleman ◽  
...  
Keyword(s):  
Phase Separation ◽  
Neurodegenerative Disease ◽  
Stress Granules ◽  
Life Time ◽  
Stress Granule ◽  
Phase Behaviour ◽  
Granule Proteins ◽  
Lateral Sclerosis ◽  
Liquid Liquid Phase Separation

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with few avenues for treatment. Many proteins implicated in ALS associate with stress granules, which are examples of liquid-like compartments formed by phase separation. Aberrant phase transition of stress granules has been implicated in disease, suggesting that modulation of phase transitions could be a possible therapeutic route. Here, we combine cell-based and protein-based screens to show that lipoamide, and its related compound lipoic acid, reduce the propensity of stress granule proteins to aggregate in vitro. More significantly, they also prevented aggregation of proteins over the life time of Caenorhabditis elegans. Observations that they prevent dieback of ALS patient-derived (FUS mutant) motor neuron axons in culture and recover motor defects in Drosophila melanogaster expressing FUS mutants suggest plausibility as effective therapeutics. Our results suggest that altering phase behaviour of stress granule proteins in the cytoplasm could be a novel route to treat ALS.

scholarly journals Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging

Cell Reports ◽  
2017 ◽  
Vol 18 (2) ◽  
pp. 454-467 ◽  
Author(s):  
Marie C. Lechler ◽  
Emily D. Crawford ◽  
Nicole Groh ◽  
Katja Widmaier ◽  
Raimund Jung ◽  
...  
Keyword(s):  
Dynamic Properties ◽  
Stress Granule ◽  
Granule Proteins

scholarly journals Genomics-guided targeting of stress granule proteins G3BP1/2 to inhibit SARS-CoV-2 propagation

2021 ◽  
Vol 190 ◽  
pp. 636-648
Author(s):  
Nemat Ali ◽  
Kartikay Prasad ◽  
Abdullah F. AlAsmari ◽  
Metab Alharbi ◽  
Summya Rashid ◽  
...  
Keyword(s):  
Stress Granule ◽  
Granule Proteins

scholarly journals Proteomic analysis reveals that MAEL, a component of nuage, interacts with stress granule proteins in cancer cells

2013 ◽  
Vol 31 (1) ◽  
pp. 342-350 ◽  
Author(s):  
LIQIN YUAN ◽  
YUZHONG XIAO ◽  
QIUZHI ZHOU ◽  
DONGMEI YUAN ◽  
BAIPING WU ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Proteomic Analysis ◽  
Stress Granule ◽  
Granule Proteins

Stimulation of phospholipase Cβ1 by Gα q promotes the assembly of stress granule proteins

2021 ◽  
Vol 14 (705) ◽  
Author(s):  
Androniqi Qifti ◽  
Lela Jackson ◽  
Ashima Singla ◽  
Osama Garwain ◽  
Suzanne Scarlata
Keyword(s):  
Stress Granule ◽  
Granule Proteins ◽  
Stimulation Of

scholarly journals Distinct Features of Stress Granule Proteins Predict Localization in Membraneless Organelles

2020 ◽  
Vol 432 (7) ◽  
pp. 2349-2368 ◽  
Author(s):  
Erich R. Kuechler ◽  
Paulina M. Budzyńska ◽  
Jonathan P. Bernardini ◽  
Jörg Gsponer ◽  
Thibault Mayor
Keyword(s):  
Stress Granule ◽  
Granule Proteins ◽  
Distinct Features

scholarly journals Comprehensive Protein Interactome Analysis of a Key RNA Helicase: Detection of Novel Stress Granule Proteins

Biomolecules ◽  
2015 ◽  
Vol 5 (3) ◽  
pp. 1441-1466 ◽  
Author(s):  
Rebecca Bish ◽  
Nerea Cuevas-Polo ◽  
Zhe Cheng ◽  
Dolores Hambardzumyan ◽  
Mathias Munschauer ◽  
...  
Keyword(s):  
Rna Helicase ◽  
Stress Granule ◽  
Protein Interactome ◽  
Granule Proteins

scholarly journals Modulation of RNA condensation by the DEAD-box protein eIF4A

2019 ◽  
Author(s):  
Devin Tauber ◽  
Gabriel Tauber ◽  
Anthony Khong ◽  
Briana Van Treeck ◽  
Jerry Pelletier ◽  
...  
Keyword(s):  
Stress Granules ◽  
Protein Aggregates ◽  
Stress Granule ◽  
List Type ◽  
Dependent Manner ◽  
Granule Formation ◽  
Dead Box ◽  
The Dead ◽  
In Cells

SUMMARYStress granules are condensates of non-translating mRNAs and proteins involved in the stress response and neurodegenerative diseases. Stress granules form in part through intermolecular RNA-RNA interactions, although the process of RNA condensation is poorly understood. In vitro, we demonstrate that RNA is effectively recruited to the surfaces of RNA or RNP condensates. We demonstrate that the DEAD-box protein eIF4A reduces RNA condensation in vitro and limits stress granule formation in cells. This defines a purpose for eIF4A to limit intermolecular RNA-RNA interactions in cells, thereby allowing for proper RNP function. These results establish an important role for DEAD-box proteins as ATP-dependent RNA chaperones that can limit the intermolecular condensation and entanglement of RNA, analogous to the function of proteins like HSP70 in combatting protein aggregates.eTOC BlurbStress granules are formed in part by the process of RNA condensation, which is mediated by and promotes trans RNA-RNA interactions. The essential DEAD-box protein and translation initiation factor eIF4A limits stress granule formation by reducing RNA condensation through its function as an ATP-dependent RNA binding protein, behaving analogously to how protein chaperones like HSP70 combat protein aggregates.HighlightsRNA condensates promote intermolecular RNA-RNA interactions at their surfaceseIF4A limits the recruitment of RNAs to stress granules in cellseIF4A reduces the nucleation of stress granules in cellsRecombinant eIF4A1 inhibits the condensation of RNA in vitro in an ATP-dependent manner

scholarly journals Stimulation of Gαq Promotes Stress Granule Formation

2019 ◽  
Author(s):  
Androniqi Qifti ◽  
Lela Jackson ◽  
Ashima Singla ◽  
Osama Garwain ◽  
Suzanne Scarlata
Keyword(s):  
Plasma Membrane ◽  
Mammalian Cells ◽  
Stress Granules ◽  
Stress Granule ◽  
Granule Formation ◽  
Adverse Conditions ◽  
Granule Proteins ◽  
Regulate Protein ◽  
As Stress ◽  
Number Of Particles

ABSTRACTDuring adverse conditions, mammalian cells regulate protein production by carefully sequestering the translation machinery in membraneless organelles referred to as stress granules. Here, we show that activation of Gαq promotes the formation of particles that contain stress granule proteins through a mechanism linked to the presence of phospholipase Cβ1 (PLCβ1). In cells, PLCβ1, the most prominent isoform of PLCβ in neuronal cells, localizes to both the cytoplasm and plasma membrane. We show that a major population of cytosolic PLCβ1 binds to stress granule proteins, such as PABPC1, eIF5A and Ago2. PLCβ1 is activated by Gαq in response to hormones and neurotransmitters and we find that activation of Gαq shifts the cytosolic population of PLCβ1 to the plasma membrane, reducing its association to stress granule proteins. The loss of cytosolic PLCβ1 is accompanied by an increase in the size and number of particles containing PABPC1, G3BP1 or Ago2, and a shift of cytosolic RNAs to larger sizes consistent with cessation of translation. Particles containing stress granule proteins are seen when the cytosolic level of PLCβ1 is lowered by siRNA or by osmotic stress but not cold, heat, oxidative or arsenite stress suggesting that their composition is distinct from those formed from other stresses. Our results fit a simple thermodynamic model in which cytosolic PLCβ1 solubilizes stress granule proteins and its movement to Gαq upon stimulation releases these particles to allow the formation of stress granules. Taken together, our studies show a link between Gαq-coupled signals and translation through stress granule formation.

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