ArticleProceedings of the National Academy of Sciences of the United States of America2015
Structural basis for mutation-induced destabilization of profilin 1 in ALS.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 80 citations in OpenAlex.
- A Missense Mutation in Close Proximity of ALS-linked PFN1 Mutations Causes Only Early-onset Paget Disease of Bone.The Journal of clinical endocrinology and metabolism · 2025Article
- Profilin and Non-Canonical Wnt Signaling: Coordinating Cytoskeletal Dynamics from Development to Disease.Journal of developmental biology · 2025Review
- Using ALS to understand profilin 1's diverse roles in cellular physiology.Cytoskeleton (Hoboken, N.J.) · 2025Review
- PARPs and ADP-ribosylation-mediated biomolecular condensates: determinants, dynamics, and disease implications.Trends in biochemical sciences · 2025Review
- Quantitative Proteomics Identifies Profilin-1 as a Pseudouridine-Binding Protein.Journal of the American Chemical Society · 2025Article
- In the Beginning: Let Hydration Be Coded in Proteins for Manifestation and Modulation by Salts and Adenosine Triphosphate.International journal of molecular sciences · 2024Review
- Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia.Nature communications · 2024Article
- Proximity Proteomics Revealed Aberrant mRNA Splicing Elicited by ALS-Linked Profilin-1 Mutants.Analytical chemistry · 2023Article
- ATP induces folding of ALS-causing C71G-hPFN1 and nascent hSOD1.Communications chemistry · 2023Article
- Anti-SOD1 Nanobodies That Stabilize Misfolded SOD1 Proteins Also Promote Neurite Outgrowth in Mutant SOD1 Human Neurons.International journal of molecular sciences · 2022Article
- Multiple roles for the cytoskeleton in ALS.Experimental neurology · 2022Review
- The Amyotrophic Lateral Sclerosis M114T PFN1 Mutation Deregulates Alternative Autophagy Pathways and Mitochondrial Homeostasis.International journal of molecular sciences · 2022Article
- Biochemical characterization of actin assembly mechanisms with ALS-associated profilin variants.European journal of cell biology · 2022Article
- Modelling amyotrophic lateral sclerosis in rodents.Nature reviews. Neuroscience · 2022Review
- Article
- Profilin 1 Induces Tumor Metastasis by Promoting Microvesicle Secretion Through the ROCK 1/p-MLC Pathway in Non-Small Cell Lung Cancer.Frontiers in pharmacology · 2022Article
- Nearly 30 Years of Animal Models to Study Amyotrophic Lateral Sclerosis: A Historical Overview and Future Perspectives.International journal of molecular sciences · 2021Review
- Low profilin 1 serum levels are associated with diabetes, family history and multivessel lesions in patients with coronary artery disease.Postepy w kardiologii interwencyjnej = Advances in interventional cardiology · 2021Article
- ALS-linked PFN1 variants exhibit loss and gain of functions in the context of formin-induced actin polymerization.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Detergent-insoluble inclusion constitutes the first pathology in PFN1 transgenic rats.Journal of neurochemistry · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-function phenotypes in cell-based assays. The source of this destabilization is illuminated by the X-ray crystal structures of several PFN1 proteins, revealing an expanded cavity near the protein core of the destabilized M114T variant. In contrast, the E117G mutation only modestly perturbs the structure and stability of PFN1, an observation that reconciles the occurrence of this mutation in the control population. These findings suggest that a destabilized form of PFN1 underlies PFN1-mediated ALS pathogenesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.