Evidence map›Paper›PMID 31474508›Full record

ArticleNeuron2019

Feedback-Driven Assembly of the Axon Initial Segment.

Amélie Fréal, Dipti Rai, Roderick P Tas, Xingxiu Pan, Eugene A Katrukha, Dieudonnée van de Willige, Riccardo Stucchi, Amol Aher, Chao Yang, A F Maarten Altelaar and 6 more

Abstract readVideo-Audio Media
In one paragraph

Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed.

  1. Review
  2. Coupling of functionality to trafficking of KCNQ2/3 potassium channels at the axon initial segment.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
  4. Review
  5. Investigation of the Neurotoxicity Mechanisms of NiInternational journal of molecular sciences · 2025
    Article
  6. Review
  7. Article
  8. Consciousness and spintronic coherence in microtubules.Communicative & integrative biology · 2025
    Article
  9. 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 · 2024
    Article
  10. Article
  11. Live imaging of excitable axonal microdomains in ankyrin-G-GFP mice.bioRxiv : the preprint server for biology · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Epilepsy geneiScience · 2023
    Article
  19. Review
  20. Extracellular Tau Oligomers Damage the Axon Initial Segment.Journal of Alzheimer's disease : JAD · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Amélie FréalCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Department of Axonal Signaling, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, the Netherlands.
Dipti RaiCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Roderick P TasCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Xingxiu PanCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Eugene A KatrukhaCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Dieudonnée van de WilligeCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Riccardo StucchiCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences and the Netherlands Proteomics Center, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Amol AherCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Chao YangCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
A F Maarten AltelaarBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences and the Netherlands Proteomics Center, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Karin VockingCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Jan Andries PostCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Martin HarterinkCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Lukas C KapiteinCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Anna AkhmanovaCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands. Electronic address: a.akhmanova@uu.nl.
Casper C HoogenraadCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Department of Neuroscience, Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: c.hoogenraad@uu.nl.

Funding

European Research Council 609822
6 · The paper itself

Abstract

The axon initial segment (AIS) is a unique neuronal compartment that plays a crucial role in the generation of action potential and neuronal polarity. The assembly of the AIS requires membrane, scaffolding, and cytoskeletal proteins, including Ankyrin-G and TRIM46. How these components cooperate in AIS formation is currently poorly understood. Here, we show that Ankyrin-G acts as a scaffold interacting with End-Binding (EB) proteins and membrane proteins such as Neurofascin-186 to recruit TRIM46-positive microtubules to the plasma membrane. Using in vitro reconstitution and cellular assays, we demonstrate that TRIM46 forms parallel microtubule bundles and stabilizes them by acting as a rescue factor. TRIM46-labeled microtubules drive retrograde transport of Neurofascin-186 to the proximal axon, where Ankyrin-G prevents its endocytosis, resulting in stable accumulation of Neurofascin-186 at the AIS. Neurofascin-186 enrichment in turn reinforces membrane anchoring of Ankyrin-G and subsequent recruitment of TRIM46-decorated microtubules. Our study reveals feedback-based mechanisms driving AIS assembly.

Indexed as

AnimalsAnkyrinsAxonal TransportAxon Initial SegmentCell Adhesion MoleculesCell Line, TumorChlorocebus aethiopsCOS CellsCytoskeletonEndocytosisFeedback, PhysiologicalHEK293 CellsHippocampusHumansMicrotubule-Associated ProteinsMicrotubulesAnk3 protein, ratAnkyrinsCell Adhesion MoleculesMicrotubule-Associated ProteinsNerve Growth FactorsNfasc protein, ratTrim46 protein, ratTripartite Motif Proteinsaxonal transportaxon initial segmentendocytosismicrotubules

Identifiers

PMID31474508
PMCPMC6839619

What OpenQuestion holds

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Registered trials

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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.