ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Inositol Hexakisphosphate Kinase-3 Regulates the Morphology and Synapse Formation of Cerebellar Purkinje Cells via Spectrin/Adducin.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- IPPK-1 and IP6 contribute to ventral nerve cord assembly in C. elegans.Developmental biology · 2025Article
- Synthesis of a New Purine Analogue Class with Antifungal Activity and Improved Potency against Fungal IPACS infectious diseases · 2025Article
- Knockout Mice as an Experimental Model to Study the Biology of Inositol Pyrophosphates.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The TrkC-PTPσ complex governs synapse maturation and anxiogenic avoidance via synaptic protein phosphorylation.The EMBO journal · 2024Article
- Deleting IP6K1 stabilizes neuronal sodium-potassium pumps and suppresses excitability.Molecular brain · 2024Article
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- Protein pyrophosphorylation by inositol phosphates: a novel post-translational modification in plants?Frontiers in plant science · 2024Review
- Article
- The Role of Inositol Hexakisphosphate Kinase in the Central Nervous System.Biomolecules · 2023Review
- TNP and its analogs: Modulation of IP6K and CYP3A4 inhibition.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Inositol hexakisphosphate kinases differentially regulate trafficking of vesicular glutamate transporters 1 and 2.Frontiers in cellular neuroscience · 2022Article
- Systematic analysis to identify transcriptome-wide dysregulation of Alzheimer's disease in genes and isoforms.Human genetics · 2021Article
- The Key Role of IPMolecules (Basel, Switzerland) · 2020Review
- Inositol Pyrophosphates: Signaling Molecules with Pleiotropic Actions in Mammals.Molecules (Basel, Switzerland) · 2020Review
- Targeting the Inositol Pyrophosphate Biosynthetic Enzymes in Metabolic Diseases.Molecules (Basel, Switzerland) · 2020Review
- Synthesis and characterization of novel isoform-selective IP6K1 inhibitors.Bioorganic & medicinal chemistry letters · 2019Article
- Adducins inhibit lung cancer cell migration through mechanisms involving regulation of cell-matrix adhesion and cadherin-11 expression.Biochimica et biophysica acta. Molecular cell research · 2019Article
- Inositol hexakisphosphate kinase 3 promotes focal adhesion turnover via interactions with dynein intermediate chain 2.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Structure-based selection of human metabolite binding P4 pocket of DRB1*15:01 and DRB1*15:03, with implications for multiple sclerosis.Genes and immunity · 2019Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The inositol hexakisphosphate kinases (IP6Ks) are the principal enzymes that generate inositol pyrophosphates. There are three IP6Ks (IP6K1, 2, and 3). Functions of IP6K1 and IP6K2 have been substantially delineated, but little is known of IP6K3's role in normal physiology, especially in the brain. To elucidate functions of IP6K3, we generated mice with targeted deletion of IP6K3. We demonstrate that IP6K3 is highly concentrated in the brain in cerebellar Purkinje cells. IP6K3 physiologically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are perturbed in IP6K3-null mutants. Consequently, IP6K3 knock-out cerebella manifest abnormalities in Purkinje cell structure and synapse number, and the mutant mice display deficits in motor learning and coordination. Thus, IP6K3 is a major determinant of cytoskeletal disposition and function of cerebellar Purkinje cells. SIGNIFICANCE STATEMENT: We identified and cloned a family of three inositol hexakisphosphate kinases (IP6Ks) that generate the inositol pyrophosphates, most notably 5-diphosphoinositol pentakisphosphate (IP7). Of these, IP6K3 has been least characterized. In the present study we generated IP6K3 knock-out mice and show that IP6K3 is highly expressed in cerebellar Purkinje cells. IP6K3-deleted mice display defects of motor learning and coordination. IP6K3-null mice manifest aberrations of Purkinje cells with a diminished number of synapses. IP6K3 interacts with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mice may mediate phenotypic features of the mutant mice. These findings afford molecular/cytoskeletal mechanisms by which the inositol polyphosphate system impacts brain function.
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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.