ArticleProceedings of the National Academy of Sciences of the United States of America2014
Aberrant calcium signaling by transglutaminase-mediated posttranslational modification of inositol 1,4,5-trisphosphate receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
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- Structural organization of p62 filaments and the cellular ultrastructure of calcium-rich p62-enwrapped lipid droplet cargo.Nature communications · 2025Article
- GPR56 signaling pathway network and its dynamics in the mesenchymal transition of glioblastoma.Journal of cell communication and signaling · 2023Article
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- Targeting calcium-mediated inter-organellar crosstalk in cardiac diseases.Expert opinion on therapeutic targets · 2022Article
- IP3R Channels in Male Reproduction.International journal of molecular sciences · 2020Review
- A C1976Y missense mutation in the mouse Ip3r1 gene leads to short-term mydriasis and unfolded protein response in the iris constrictor muscles.Experimental animals · 2020Article
- Endogenous mouse huntingtin is highly abundant in cranial nerve nuclei, co-aggregates to Abeta plaques and is induced in reactive astrocytes in a transgenic mouse model of Alzheimer's disease.Acta neuropathologica communications · 2019Article
- Structure and Function of IPCold Spring Harbor perspectives in biology · 2019Review
- Reduced presynaptic vesicle stores mediate cellular and network plasticity defects in an early-stage mouse model of Alzheimer's disease.Molecular neurodegeneration · 2019Article
- High and Low Levels of an NTRK2-Driven Genetic Profile Affect Motor- and Cognition-Associated Frontal Gray Matter in Prodromal Huntington's Disease.Brain sciences · 2018Article
- Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic.Molecular neurobiology · 2017Review
- Transglutaminase 2 mediates UV-induced skin inflammation by enhancing inflammatory cytokine production.Cell death & disease · 2017Article
- IPProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Inositol 1,4,5-trisphosphate receptors and their protein partners as signalling hubs.The Journal of physiology · 2016Review
- Gender differences in white matter pathology and mitochondrial dysfunction in Alzheimer's disease with cerebrovascular disease.Molecular brain · 2016Article
- Shared functional defect in IP₃R-mediated calcium signaling in diverse monogenic autism syndromes.Translational psychiatry · 2015Article
- Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inositol 1,4,5-trisphosphate receptor (IP3R) in the endoplasmic reticulum mediates calcium signaling that impinges on intracellular processes. IP3Rs are allosteric proteins comprising four subunits that form an ion channel activated by binding of IP3 at a distance. Defective allostery in IP3R is considered crucial to cellular dysfunction, but the specific mechanism remains unknown. Here we demonstrate that a pleiotropic enzyme transglutaminase type 2 targets the allosteric coupling domain of IP3R type 1 (IP3R1) and negatively regulates IP3R1-mediated calcium signaling and autophagy by locking the subunit configurations. The control point of this regulation is the covalent posttranslational modification of the Gln2746 residue that transglutaminase type 2 tethers to the adjacent subunit. Modification of Gln2746 and IP3R1 function was observed in Huntington disease models, suggesting a pathological role of this modification in the neurodegenerative disease. Our study reveals that cellular signaling is regulated by a new mode of posttranslational modification that chronically and enzymatically blocks allosteric changes in the ligand-gated channels that relate to disease states.
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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.