ArticleTranslational psychiatry2018
Disruption of the psychiatric risk gene Ankyrin 3 enhances microtubule dynamics through GSK3/CRMP2 signaling.
Article in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Lithium restores inhibitory function and neuronal excitability through GSK-3β inhibition in a bipolar disorder-associated Ank3 variant mouse model.Neuropharmacology · 2025Article
- Bioinformatics Analysis of Persistent Dysregulated Expression of Genes Involved in HCV-Induced Neurological Disorders and Liver Injuries After DAA Treatment Through Weighted Gene Co-Expression Network Analysis.Health science reports · 2025Article
- Identification of Expression Quantitative Trait Loci (eQTL) for Adipose-Specific Regulatory Mechanisms in Hanwoo (Korean Cattle).Animals : an open access journal from MDPI · 2025Article
- Identification of a 13-Gene Immune Signature in Liver Fibrosis Reveals GABRE as a Novel Candidate Biomarker.International journal of molecular sciences · 2025Article
- Uncovering the ferroptosis related mechanism of laduviglusib in the cell-type-specific targets of the striatum in Huntington's disease.BMC genomics · 2024Article
- Neurite outgrowth deficits caused by rare PLXNB1 mutation in pediatric bipolar disorder.Molecular psychiatry · 2023Article
- Lithium rescues dendritic abnormalities in Ank3 deficiency models through the synergic effects of GSK3β and cyclic AMP signaling pathways.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Clinical case report: mosaicCold Spring Harbor molecular case studies · 2023Article
- Axonal transport deficits in neuropsychiatric disorders.Molecular and cellular neurosciences · 2022Article
- Case report: Somatic mutations in microtubule dynamics-associated genes in patients with WNT-medulloblastoma tumors.Frontiers in oncology · 2022Article
- Known and Unexplored Post-Translational Modification Pathways in Schizophrenia.Advances in experimental medicine and biology · 2022Article
- Inhibition of glycogen synthase kinase 3 by lithium, a mechanism in search of specificity.Frontiers in molecular neuroscience · 2022Review
- A Rare Variant ofFrontiers in neurology · 2021Article
- Translational genomics and beyond in bipolar disorder.Molecular psychiatry · 2021Review
- Pharmacological Manipulation of Wnt/β-Catenin Signaling Pathway in Human Neural Precursor Cells Alters Their Differentiation Potential and Neuronal Yield.Frontiers in molecular neuroscience · 2021Article
- Advances toward precision medicine for bipolar disorder: mechanisms & molecules.Molecular psychiatry · 2021Review
- Identification of candidate genetic variants and altered protein expression in neural stem and mature neural cells support altered microtubule function to be an essential component in bipolar disorder.Translational psychiatry · 2020Article
- Cargo hold and delivery: Ankyrins, spectrins, and their functional patterning of neurons.Cytoskeleton (Hoboken, N.J.) · 2020Review
- Discovery of suppressors of CRMP2 phosphorylation reveals compounds that mimic the behavioral effects of lithium on amphetamine-induced hyperlocomotion.Translational psychiatry · 2020Article
- Mapping axon initial segment structure and function by multiplexed proximity biotinylation.Nature communications · 2020Article
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
The ankyrin 3 gene (ANK3) is a well-established risk gene for psychiatric illness, but the mechanisms underlying its pathophysiology remain elusive. We examined the molecular effects of disrupting brain-specific Ank3 isoforms in mouse and neuronal model systems. RNA sequencing of hippocampus from Ank3+/- and Ank3+/+ mice identified altered expression of 282 genes that were enriched for microtubule-related functions. Results were supported by increased expression of microtubule end-binding protein 3 (EB3), an indicator of microtubule dynamics, in Ank3+/- mouse hippocampus. Live-cell imaging of EB3 movement in primary neurons from Ank3+/- mice revealed impaired elongation of microtubules. Using a CRISPR-dCas9-KRAB transcriptional repressor in mouse neuro-2a cells, we determined that repression of brain-specific Ank3 increased EB3 expression, decreased tubulin acetylation, and increased the soluble:polymerized tubulin ratio, indicating enhanced microtubule dynamics. These changes were rescued by inhibition of glycogen synthase kinase 3 (GSK3) with lithium or CHIR99021, a highly selective GSK3 inhibitor. Brain-specific Ank3 repression in neuro-2a cells increased GSK3 activity (reduced inhibitory phosphorylation) and elevated collapsin response mediator protein 2 (CRMP2) phosphorylation, a known GSK3 substrate and microtubule-binding protein. Pharmacological inhibition of CRMP2 activity attenuated the rescue of EB3 expression and tubulin polymerization in Ank3-repressed cells by lithium or CHIR99021, suggesting microtubule instability induced by Ank3 repression is dependent on CRMP2 activity. Taken together, our data indicate that ANK3 functions in neuronal microtubule dynamics through GSK3 and its downstream substrate CRMP2. These findings reveal cellular and molecular mechanisms underlying brain-specific ANK3 disruption that may be related to its role in psychiatric illness.
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