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bioRxiv · 10.1101/022962

Nanoscale architecture of the axon initial segment reveals an organized and robust scaffold

Christophe Leterrier·Jean Potier·Ghislaine Caillol·Claire Debarnot·Fanny Rueda Boroni·Bénédicte Dargent
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Abstract

The Axon Initial Segment [AIS], located within the first 30 m of the axon, has two essential roles in generating action potentials and maintaining axonal identity. AIS assembly depends on a {beta}IV-spectrin / ankyrin G scaffold, but its macromolecular arrangement is not well understood. Here we quantitatively determined the AIS nanoscale architecture using STo-chastic Optical Reconstruction Microscopy [STORM]. First we directly demonstrate that the 190-nm periodicity of the AIS submembrane lattice results from longitudinal, head-to-head {beta}IV-spectrin molecules connecting actin rings. Using multicolor 3D-STORM, we resolve the nanoscale organization of ankyrin G: its aminoterminus associates with the submembrane lattice, whereas the carboxyterminus radially extends (~32 nm on average) toward the cytosol. This AIS nano-architecture is highly resistant to cytoskeletal perturbations, advocating its role in structural stabilization. Our findings provide a comprehensive view of the AIS molecular architecture, and will help understanding the crucial physiological functions of this compartment.

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Christophe Leterrier, Jean Potier, Ghislaine Caillol, Claire Debarnot, Fanny Rueda Boroni, Bénédicte Dargent. 2015-07-21. Nanoscale architecture of the axon initial segment reveals an organized and robust scaffold. https://doi.org/10.1101/022962

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