ArticleHuman molecular genetics2012
High-content RNAi screening identifies the Type 1 inositol triphosphate receptor as a modifier of TDP-43 localization and neurotoxicity.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- Reduction of RAD23A extends lifespan and mitigates pathology in a mouse model of TDP-43 proteinopathy.Nature communications · 2026Article
- MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.Molecular neurobiology · 2026Review
- DNA-damage dependent isoform switching modulates RIF1 DNA repair complex assembly and phase separation.The Journal of biological chemistry · 2025Article
- RNA-Binding Proteins: A Role in Neurotoxicity?Neurotoxicity research · 2023Review
- New regulators of the tetracycline-inducible gene expression system identified by chemical and genetic screens.FEBS open bio · 2022Article
- Emerging Therapies and Novel Targets for TDP-43 Proteinopathy in ALS/FTD.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Review
- Rapid in vitro quantification of TDP-43 and FUS mislocalisation for screening of gene variants implicated in frontotemporal dementia and amyotrophic lateral sclerosis.Scientific reports · 2021Article
- Interplay of RNA-Binding Proteins and microRNAs in Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- Regulation of longevity by depolarization-induced activation of PLC-β-IPProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Amyotrophic Lateral Sclerosis Genes inInternational journal of molecular sciences · 2021Review
- Cytosolic calcium regulates cytoplasmic accumulation of TDP-43 through Calpain-A and Importin α3.eLife · 2020Article
- Traffic jam at the nuclear pore: All roads lead to nucleocytoplasmic transport defects in ALS/FTD.Neurobiology of disease · 2020Review
- Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update.Journal of clinical medicine · 2020Review
- Genome wide analysis reveals heparan sulfate epimerase modulates TDP-43 proteinopathy.PLoS genetics · 2019Article
- Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic.Molecular neurobiology · 2017Review
- High content analysis in amyotrophic lateral sclerosis.Molecular and cellular neurosciences · 2017Review
- A fruitful endeavor: modeling ALS in the fruit fly.Brain research · 2015Review
- Opposing roles of p38 and JNK in a Drosophila model of TDP-43 proteinopathy reveal oxidative stress and innate immunity as pathogenic components of neurodegeneration.Human molecular genetics · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cytosolic aggregation of the nuclear RNA-binding protein (RBP) TDP-43 (43 kDa TAR DNA-binding domain protein) is a suspected direct or indirect cause of motor neuron deterioration in amyotrophic lateral sclerosis (ALS). In this study, we implemented a high-content, genome-wide RNAi screen to identify pathways controlling TDP-43 nucleocytoplasmic shuttling. We identified ∼60 genes whose silencing increased the cytosolic localization of TDP-43, including nuclear pore complex components and regulators of G2/M cell cycle transition. In addition, we identified the type 1 inositol-1,4,5-trisphosphate (IP3) receptor (ITPR1), an IP3-gated, endoplasmic reticulum (ER)-resident Ca(2+) channel, as a strong modulator of TDP-43 nucleocytoplasmic shuttling. Knockdown or chemical inhibition of ITPR1 induced TDP-43 nuclear export in immortalized cells and primary neurons and strongly potentiated the recruitment of TDP-43 to Ubiquilin-positive autophagosomes, suggesting that diminished ITPR1 function leads to autophagosomal clearance of TDP-43. The functional significance of the TDP-43-ITPR1 genetic interaction was tested in Drosophila, where mutant alleles of ITPR1 were found to significantly extended lifespan and mobility of flies expressing TDP-43 under a motor neuron driver. These combined findings implicate IP3-gated Ca(2+) as a key regulator of TDP-43 nucleoplasmic shuttling and proteostasis and suggest pharmacologic inhibition of ITPR1 as a strategy to combat TDP-43-induced neurodegeneration in vivo.
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.