ArticleProceedings of the National Academy of Sciences of the United States of America2019
Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Pooled it
- Surveying alternative transcripts of disease-associated genes and their cell type specificity - a case study with ANK3.Translational psychiatry · 2026Article
- A functional role for Septin-2 in the maintenance of the axon initial segment and in human cognitive development.Brain : a journal of neurology · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- A neuron type-specific microexon in Ank3/ankyrin-G modulates calcium activity and neuronal excitability.Nature communications · 2026Article
- A neuron type-specific microexon inbioRxiv : the preprint server for biology · 2025Article
- Impaired AIS plasticity in ankyrin-G mutant mice alters cortical excitability and behavior.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Loss of ANK3 Function Causes a Recessive Neurodevelopmental Disorder with Cerebellar Ataxia.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Cytoskeletal scaffolding of NaCurrent opinion in cell biology · 2025Review
- Regulation of neuronal ankyrin localization and function by post-translational modifications.Biochemical Society transactions · 2025Review
- Alterations in the axon initial segment plasticity is involved in early pathogenesis in Alzheimer's disease.MedComm · 2024Article
- The phenotypic and genotypic spectrum of individuals with mono- or biallelic ANK3 variants.Clinical genetics · 2024Article
- Specific and Plastic: Chandelier Cell-to-Axon Initial Segment Connections in Shaping Functional Cortical Network.Neuroscience bulletin · 2024Review
- MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination.Journal of cell science · 2024Article
- Article
- Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex.Neuroscience bulletin · 2023Article
- Review
- Spectrins: molecular organizers and targets of neurological disorders.Nature reviews. Neuroscience · 2023Review
- Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome.Molecular psychiatry · 2023Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Giant ankyrin-G (gAnkG) coordinates assembly of axon initial segments (AISs), which are sites of action potential generation located in proximal axons of most vertebrate neurons. Here, we identify a mechanism required for normal neural development in humans that ensures ordered recruitment of gAnkG and β4-spectrin to the AIS. We identified 3 human neurodevelopmental missense mutations located in the neurospecific domain of gAnkG that prevent recruitment of β4-spectrin, resulting in a lower density and more elongated pattern for gAnkG and its partners than in the mature AIS. We found that these mutations inhibit transition of gAnkG from a closed configuration with close apposition of N- and C-terminal domains to an extended state that is required for binding and recruitment of β4-spectrin, and normally occurs early in development of the AIS. We further found that the neurospecific domain is highly phosphorylated in mouse brain, and that phosphorylation at 2 sites (S1982 and S2619) is required for the conformational change and for recruitment of β4-spectrin. Together, these findings resolve a discrete intermediate stage in formation of the AIS that is regulated through phosphorylation of the neurospecific domain of gAnkG.
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Registered trials
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