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Updated: Aug 22, 2026

Use of Primary Cultured Hippocampal Neurons to Study the Assembly of Axon Initial Segments
Published on: February 12, 2021
BetaIVSigma1 spectrin stabilizes the nodes of Ranvier and axon initial segments
Sandra Lacas-Gervais1, Jun Guo, Nicola Strenzke
1Medical School, University of Technology-Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Abstract:
Saltatory electric conduction requires clustered voltage-gated sodium channels (VGSCs) at axon initial segments (AIS) and nodes of Ranvier (NR). A dense membrane undercoat is present at these sites, which is thought to be key for the focal accumulation of channels. Here, we prove that betaIVSigma1 spectrin, the only betaIV spectrin with an actin-binding domain, is an essential component of this coat. Specifically, betaIVSigma1 coexists with betaIVSigma6 at both AIS and NR, being the predominant spectrin at AIS. Removal of betaIVSigma1 alone causes the disappearance of the nodal coat, an increased diameter of the NR, and the presence of dilations filled with organelles. Moreover, in myelinated cochlear afferent fibers, VGSC and ankyrin G clusters appear fragmented. These ultrastructural changes can explain the motor and auditory neuropathies present in betaIVSigma1 -/- mice and point to the betaIVSigma1 spectrin isoform as a master-stabilizing factor of AIS/NR membranes.
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