ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2022
Axon Initial Segments Are Required for Efficient Motor Neuron Axon Regeneration and Functional Recovery of Synapses.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 14 citations in OpenAlex.
- Volume electron microscopy in axon regeneration research: insights into mitochondria, endoplasmic reticulum, and membrane contacts.Frontiers in neural circuits · 2026Review
- Absence of the axon initial segment in sensory neuron enhances resistance to amyotrophic lateral sclerosis.Brain : a journal of neurology · 2025Article
- The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.Nature communications · 2025Article
- Potassium channel clustering: mechanisms shaping axonal excitability.Frontiers in cellular neuroscience · 2025Review
- 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
- The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.bioRxiv : the preprint server for biology · 2024Article
- Postsynaptic β1 spectrin maintains NaThe Journal of physiology · 2024Article
- Thalamic Neuron Resilience during Osmotic Demyelination Syndrome (ODS) Is Revealed by Primary Cilium Outgrowth and ADP-ribosylation factor-like protein 13B Labeling in Axon Initial Segment.International journal of molecular sciences · 2023Article
- Three-dimensional ultrastructure analysis of organelles in injured motor neuron.Anatomical science international · 2023Review
- Neurofilament accumulations in amyotrophic lateral sclerosis patients' motor neurons impair axonal initial segment integrity.Cellular and molecular life sciences : CMLS · 2023Article
- The Axon Initial Segment Plays a Dynamic Role in Peripheral Motor Neuron Synapse Regeneration following Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Microfluidic Platforms Promote Polarization of Human-Derived Retinal Ganglion Cells That Model Axonopathy.Translational vision science & technology · 2023Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
The axon initial segment (AIS) generates action potentials and maintains neuronal polarity by regulating the differential trafficking and distribution of proteins, transport vesicles, and organelles. Injury and disease can disrupt the AIS, and the subsequent loss of clustered ion channels and polarity mechanisms may alter neuronal excitability and function. However, the impact of AIS disruption on axon regeneration after injury is unknown. We generated male and female mice with AIS-deficient multipolar motor neurons by deleting AnkyrinG, the master scaffolding protein required for AIS assembly and maintenance. We found that after nerve crush, neuromuscular junction reinnervation was significantly delayed in AIS-deficient motor neurons compared with control mice. In contrast, loss of AnkyrinG from pseudo-unipolar sensory neurons did not impair axon regeneration into the intraepidermal nerve fiber layer. Even after AIS-deficient motor neurons reinnervated the neuromuscular junction, they failed to functionally recover because of reduced synaptic vesicle protein 2 at presynaptic terminals. In addition, mRNA trafficking was disrupted in AIS-deficient axons. Our results show that, after nerve injury, an intact AIS is essential for efficient regeneration and functional recovery of axons in multipolar motor neurons. Our results also suggest that loss of polarity in AIS-deficient motor neurons impairs the delivery of axonal proteins, mRNAs, and other cargoes necessary for regeneration. Thus, therapeutic strategies for axon regeneration must consider preservation or reassembly of the AIS.
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