ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Profilin 1 associates with stress granules and ALS-linked mutations alter stress granule dynamics.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 146 citations in OpenAlex.
- Targeted stress granule regulation by engineering a non-catalytic O-GlcNAc transferase.Nature communications · 2026Article
- NEDD8, stress granules, and amyotrophic lateral sclerosis: unveiling the therapeutic potential of the NEDP1 protease.Essays in biochemistry · 2025Review
- The Central Role of Actin in Creutzfeldt-Jakob Disease: Unlocking Therapeutic Pathways.Molecular neurobiology · 2025Review
- TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes.Nature neuroscience · 2025Article
- Endogenous retrovirus-like proteins recruit UBQLN2 to stress granules and shape their functional biology.Science advances · 2025Article
- Using ALS to understand profilin 1's diverse roles in cellular physiology.Cytoskeleton (Hoboken, N.J.) · 2025Review
- Quantitative Proteomics Identifies Profilin-1 as a Pseudouridine-Binding Protein.Journal of the American Chemical Society · 2025Article
- Stress Granule Induction in Rat Retinas Damaged by Constant LED Light.Investigative ophthalmology & visual science · 2025Article
- Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.Neuroscience bulletin · 2024Review
- The actin binding protein profilin 1 localizes inside mitochondria and is critical for their function.EMBO reports · 2024Article
- OptoProfilin: A Single Component Biosensor of Applied Cellular Stress.Chembiochem : a European journal of chemical biology · 2024Article
- Identification of small molecule inhibitors of G3BP-driven stress granule formation.The Journal of cell biology · 2024Article
- TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes.bioRxiv : the preprint server for biology · 2024Article
- Physiology and pharmacological targeting of phase separation.Journal of biomedical science · 2024Review
- Quantitative analysis of septin Cdc10 & Cdc3-associated proteome during stress response in the fungal pathogen Cryptococcus neoformans.PloS one · 2024Article
- OptoProfilin: A Single Component Biosensor of Applied Cellular Stress.bioRxiv : the preprint server for biology · 2023Article
- RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS.Science advances · 2023Article
- In situ visualization of m6A sites in cellular mRNAs.Nucleic acids research · 2023Article
- Proximity Proteomics Revealed Aberrant mRNA Splicing Elicited by ALS-Linked Profilin-1 Mutants.Analytical chemistry · 2023Article
- Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the PFN1 gene encoding profilin 1 are a rare cause of familial amyotrophic lateral sclerosis (ALS). Profilin 1 is a well studied actin-binding protein but how PFN1 mutations cause ALS is unknown. The budding yeast, Saccharomyces cerevisiae, has one PFN1 ortholog. We expressed the ALS-linked profilin 1 mutant proteins in yeast, demonstrating a loss of protein stability and failure to restore growth to profilin mutant cells, without exhibiting gain-of-function toxicity. This model provides for simple and rapid screening of novel ALS-linked PFN1 variants. To gain insight into potential novel roles for profilin 1, we performed an unbiased, genome-wide synthetic lethal screen with yeast cells lacking profilin (pfy1Δ). Unexpectedly, deletion of several stress granule and processing body genes, including pbp1Δ, were found to be synthetic lethal with pfy1Δ. Mutations in ATXN2, the human ortholog of PBP1, are a known ALS genetic risk factor and ataxin 2 is a stress granule component in mammalian cells. Given this genetic interaction and recent evidence linking stress granule dynamics to ALS pathogenesis, we hypothesized that profilin 1 might also associate with stress granules. Here we report that profilin 1 and related protein profilin 2 are novel stress granule-associated proteins in mouse primary cortical neurons and in human cell lines and that ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis.
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