ArticleHuman molecular genetics2011
Mutant huntingtin causes defective actin remodeling during stress: defining a new role for transglutaminase 2 in neurodegenerative disease.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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
79 citing papers in PubMed, 133 citations in OpenAlex.
- A study of molecular changes relating to energy metabolism and cellular stress in people with Huntington's disease: looking for biomarkers.Journal of bioenergetics and biomembranes · 2013Trial
- Alterations of actin in aging.Journal of cell science · 2026Review
- Molecular and imaging biomarker responses to brain mutant HTT lowering in a mouse model of Huntington disease.Molecular therapy. Nucleic acids · 2025Article
- Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization.Science advances · 2025Article
- CellPHIE: Integrating Pathway Discovery With Pooled Profiling of Perturbations Uncovers Pathways of Huntington's Disease, Including Genetic Modifiers of Neuronal Development and Morphology.bioRxiv : the preprint server for biology · 2025Article
- Reducing Cofilin dosage makes embryos resilient to heat stress.bioRxiv : the preprint server for biology · 2025Article
- Pathogenetic Contributions and Therapeutic Implications of Transglutaminase 2 in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Branching out in different directions: Emerging cellular functions for the Arp2/3 complex and WASP-family actin nucleation factors.European journal of cell biology · 2023Article
- Characterization of huntingtin interactomes and their dynamic responses in living cells by proximity proteomics.Journal of neurochemistry · 2023Article
- Perturbed actin cap as a new personalized biomarker in primary fibroblasts of Huntington's disease patients.Frontiers in cell and developmental biology · 2023Article
- Filamentous nuclear actin regulation of PML NBs during the DNA damage response is deregulated by prelamin A.Cell death & disease · 2022Article
- A Progressive Loss of phosphoSer138-Profilin Aligns with Symptomatic Course in the R6/2 Mouse Model of Huntington's Disease: Possible Sex-Dependent Signaling.Cellular and molecular neurobiology · 2022Article
- Antisense Oligonucleotide Therapy: From Design to the Huntington Disease Clinic.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- Recent Microscopy Advances and the Applications to Huntington's Disease Research.Journal of Huntington's disease · 2022Review
- SUMOylation of Nuclear γ-Actin by SUMO2 supports DNA Damage Repair against Myocardial Ischemia-Reperfusion Injury.International journal of biological sciences · 2022Article
- Investigation of the Potential Mechanisms Underlying Nuclear F-Actin Organization in Ovarian Cancer Cells by High-Throughput Screening in Combination With Deep Learning.Frontiers in cell and developmental biology · 2022Article
- Cytoskeletal dysregulation and neurodegenerative disease: Formation, monitoring, and inhibition of cofilin-actin rods.Frontiers in cellular neuroscience · 2022Review
- Article
- Review
- Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Huntington's disease (HD) is caused by an expanded CAG tract in the Interesting transcript 15 (IT15) gene encoding the 350 kDa huntingtin protein. Cellular stresses can trigger the release of huntingtin from the endoplasmic reticulum, allowing huntingtin nuclear entry. Here, we show that endogenous, full-length huntingtin localizes to nuclear cofilin-actin rods during stress and is required for the proper stress response involving actin remodeling. Mutant huntingtin induces a dominant, persistent nuclear rod phenotype similar to that described in Alzheimer's disease for cytoplasmic cofilin-actin rods. Using live cell temporal studies, we show that this stress response is similarly impaired when mutant huntingtin is present, or when normal huntingtin levels are reduced. In clinical lymphocyte samples from HD patients, we have quantitatively detected cross-linked complexes of actin and cofilin with complex formation varying in correlation with disease progression. By live cell fluorescence lifetime imaging measurement-Förster resonant energy transfer studies and western blot assays, we quantitatively observed that stress-activated tissue transglutaminase 2 (TG2) is responsible for the actin-cofilin covalent cross-linking observed in HD. These data support a direct role for huntingtin in nuclear actin re-organization, and describe a new pathogenic mechanism for aberrant TG2 enzymatic hyperactivity in neurodegenerative diseases.
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.