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 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.

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 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 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.

scholarly journals Zika Virus Subverts Stress Granules To Promote and Restrict Viral Gene Expression

2019 ◽  
Vol 93 (12) ◽  
Author(s):  
Gaston Bonenfant ◽  
Nina Williams ◽  
Rachel Netzband ◽  
Megan C. Schwarz ◽  
Matthew J. Evans ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Development ◽  
Zika Virus ◽  
Viral Gene Expression ◽  
Stress Granules ◽  
Stress Granule ◽  
Viral Gene ◽  
Zikv Infection ◽  
Virion Production ◽  
Granule Proteins

ABSTRACTFlaviviruses limit the cell stress response by preventing the formation of stress granules (SGs) and modulate viral gene expression by subverting different proteins involved in the stress granule pathway. In this study, we investigated the formation of stress granules during Zika virus (ZIKV) infection and the role stress granule proteins play during the viral life cycle. Using immunofluorescence and confocal microscopy, we determined that ZIKV disrupted the formation of arsenite-induced stress granules and changed the subcellular distribution, but not the abundance or integrity, of stress granule proteins. We also investigated the role of different stress granule proteins in ZIKV infection by using target-specific short interfering RNAs to deplete Ataxin2, G3BP1, HuR, TIA-1, TIAR, and YB1. Knockdown of TIA-1 and TIAR affected ZIKV protein and RNA levels but not viral titers. Conversely, depletion of Ataxin2 and YB1 decreased virion production despite having only a small effect on ZIKV protein expression. Notably, however, depletion of G3BP1 and HuR decreased and increased ZIKV gene expression and virion production, respectively. Using an MR766GaussiaLuciferase reporter genome together with knockdown and overexpression assays, G3BP1 and HuR were found to modulate ZIKV replication. These data indicate that ZIKV disrupts the formation of stress granules by sequestering stress granule proteins required for replication, where G3BP1 functions to promote ZIKV infection while HuR exhibits an antiviral effect. The results of ZIKV relocalizing and subverting select stress granule proteins might have broader consequences on cellular RNA homeostasis and contribute to cellular gene dysregulation and ZIKV pathogenesis.IMPORTANCEMany viruses inhibit SGs. In this study, we observed that ZIKV restricts SG assembly, likely by relocalizing and subverting specific SG proteins to modulate ZIKV replication. This ZIKV-SG protein interaction is interesting, as many SG proteins are also known to function in neuronal granules, which are critical in neural development and function. Moreover, dysregulation of different SG proteins in neurons has been shown to play a role in the progression of neurodegenerative diseases. The likely consequences of ZIKV modulating SG assembly and subverting specific SG proteins are alterations to cellular mRNA transcription, splicing, stability, and translation. Such changes in cellular ribostasis could profoundly affect neural development and contribute to the devastating developmental and neurological anomalies observed following intrauterine ZIKV infection. Our study provides new insights into virus-host interactions and the identification of the SG proteins that may contribute to the unusual pathogenesis associated with this reemerging arbovirus.

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