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Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, we used ascorbate peroxidase (APEX) proximity labeling, mass spectrometry, and immunofluorescence to identify ∼150 previously unknown human SG components. A highly integrated, pre-existing SG protein interaction network in unstressed cells facilitates rapid coalescence into larger SGs. Approximately 20% of SG diversity is stress or cell-type dependent, with neuronal SGs displaying a particularly complex repertoire of proteins enriched in chaperones and autophagy factors. Strengthening the link between SGs and neurodegeneration, we demonstrate aberrant dynamics, composition, and subcellular distribution of SGs in cells from amyotrophic lateral sclerosis (ALS) patients. Using three Drosophila ALS/FTD models, we identify SG-associated modifiers of neurotoxicity in vivo. Altogether, our results highlight SG proteins as central to understanding and ultimately targeting neurodegeneration.
Pubmed ID: 29373831 RIS Download
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A web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.
View all literature mentionsSoftware platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.
View all literature mentionsMass spectrometry Interactive Virtual Environment (MassIVE) is a community resource developed by the NIH-funded Center for Computational Mass Spectrometry to promote the global, free exchange of mass spectrometry data. Data repository for proteomics data.
View all literature mentionsDatabase of cell lines with each expressing a tagged version of a protein from the ORFeome collection. The overarching project goal is to determine protein interactions for every member of the collection.
View all literature mentionsThis monoclonal targets Mouse Neurofilament H PhosphoDetect? Clone SMI-31
View all literature mentionsThis polyclonal targets ISL1
View all literature mentionsThis monoclonal targets Nestin
View all literature mentionsThis polyclonal targets GABARAPL2
View all literature mentionsThis monoclonal targets VBP1
View all literature mentionsThis polyclonal targets TARDBP polyclonal antibody (A01)
View all literature mentionsThis polyclonal targets TIA-1 (C-20)
View all literature mentionsThis monoclonal targets Mouse G3BP1 Clone 14E5-G9
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02496}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00428}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; PBac{w[+mC]=PB}Unr[c01923] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[67c23]; P{y[+mDint2] w[+mC]=EPgy2}Unr[EY10356] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00140}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01476}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01247}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=EP}Psi[G5862] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMJ23346}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1]; P{y[+mDint2] w[BR.E.BR]=SUPor-P}lig[KG08209]/CyO; ry[506] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; PBac{w[+mC]=RB}lig[e04268]/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01478}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01477}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; PBac{w[+mC]=WH}Hrb27C[f04375]/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.GL00205}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02884}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[67c23]; P{y[+mDint2] w[+mC]=EPgy2}bel[EY08943] from BDSC.
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