ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Cooperative Interactions between 480 kDa Ankyrin-G and EB Proteins Assemble the Axon Initial Segment.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 78 citations in OpenAlex.
- 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
- Cytoskeletal scaffolding of NaCurrent opinion in cell biology · 2025Review
- Ankyrin-G and Its Binding Partners in Neurons: Orchestrating the Molecular Structure of the Axon Initial Segment.Biomolecules · 2025Review
- Tsc1 deletion in Purkinje neurons disrupts the axon initial segment, impairing excitability and cerebellar function.Neurobiology of disease · 2025Article
- Axon initial segment structure and function in health and disease.Physiological reviews · 2025Review
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- Unveiling the cell biology of hippocampal neurons with dendritic axon origin.The Journal of cell biology · 2025Article
- TRIM46 Is Required for Microtubule Fasciculation In Vivo But Not Axon Specification or Axon Initial Segment Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Live imaging of excitable axonal microdomains in ankyrin-G-GFP mice.bioRxiv : the preprint server for biology · 2024Article
- The Role ofCirculation research · 2024Article
- Microtubule plus-end tracking proteins: novel modulators of cardiac sodium channels and arrhythmogenesis.Cardiovascular research · 2023Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- CDK5/p35-Dependent Microtubule Reorganization Contributes to Homeostatic Shortening of the Axon Initial Segment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling.Science advances · 2022Article
- Roles and mechanisms of ankyrin-G in neuropsychiatric disorders.Experimental & molecular medicine · 2022Review
- Microtubule polarity is instructive for many aspects of neuronal polarity.Developmental biology · 2022Article
- Case report: Somatic mutations in microtubule dynamics-associated genes in patients with WNT-medulloblastoma tumors.Frontiers in oncology · 2022Article
- Formin Activity and mDia1 Contribute to Maintain Axon Initial Segment Composition and Structure.Molecular neurobiology · 2021Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The axon initial segment (AIS) is required for generating action potentials and maintaining neuronal polarity. Significant progress has been made in deciphering the basic building blocks composing the AIS, but the underlying mechanisms required for AIS formation remains unclear. The scaffolding protein ankyrin-G is the master-organizer of the AIS. Microtubules and their interactors, particularly end-binding proteins (EBs), have emerged as potential key players in AIS formation. Here, we show that the longest isoform of ankyrin-G (480AnkG) selectively associates with EBs via its specific tail domain and that this interaction is crucial for AIS formation and neuronal polarity in cultured rodent hippocampal neurons. EBs are essential for 480AnkG localization and stabilization at the AIS, whereas 480AnkG is required for the specific accumulation of EBs in the proximal axon. Our findings thus provide a conceptual framework for understanding how the cooperative relationship between 480AnkG and EBs induces the assembly of microtubule-AIS structures in the proximal axon. SIGNIFICANCE STATEMENT: Neuronal polarity is crucial for the proper function of neurons. The assembly of the axon initial segment (AIS), which is the hallmark of early neuronal polarization, relies on the longest 480 kDa ankyrin-G isoform. The microtubule cytoskeleton and its interacting proteins were suggested to be early key players in the process of AIS formation. In this study, we show that the crosstalk between 480 kDa ankyrin-G and the microtubule plus-end tracking proteins, EBs, at the proximal axon is decisive for AIS assembly and neuronal polarity. Our work thus provides insight into the functional mechanisms used by 480 kDa ankyrin-G to drive the AIS formation and thereby to establish neuronal polarity.
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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.