Axon initial segments: structure, function, and disease

Ann N Y Acad Sci. 2018 May;1420(1):46-61. doi: 10.1111/nyas.13718. Epub 2018 May 11.


The axon initial segment (AIS) is located at the proximal axon and is the site of action potential initiation. This reflects the high density of ion channels found at the AIS. Adaptive changes to the location and length of the AIS can fine-tune the excitability of neurons and modulate plasticity in response to activity. The AIS plays an important role in maintaining neuronal polarity by regulating the trafficking and distribution of proteins that function in somatodendritic or axonal compartments of the neuron. In this review, we provide an overview of the AIS cytoarchitecture, mechanism of assembly, and recent studies revealing mechanisms of differential transport at the AIS that maintain axon and dendrite identities. We further discuss how genetic mutations in AIS components (i.e., ankyrins, ion channels, and spectrins) and injuries may cause neurological disorders.

Keywords: axon; cytoskeleton; ion channel; polarity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Action Potentials / physiology
  • Ankyrins / genetics*
  • Axon Initial Segment / pathology*
  • Axon Initial Segment / ultrastructure
  • Cell Polarity / physiology
  • Humans
  • Ion Channels / genetics
  • Ion Channels / physiology
  • Nervous System Diseases / pathology*
  • Neurons / physiology
  • Protein Transport / physiology*
  • Ranvier's Nodes / physiology


  • ANK3 protein, human
  • Ankyrins
  • Ion Channels