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

View ORCID ProfileChristophe Leterrier, View ORCID ProfileJean Potier, View ORCID ProfileGhislaine Caillol, View ORCID ProfileClaire Debarnot, View ORCID ProfileFanny Rueda Boroni, View ORCID ProfileBénédicte Dargent
doi: https://doi.org/10.1101/022962
Christophe Leterrier
1Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 cedex 15, Marseille, France
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  • For correspondence: christophe.leterrier@univ-amu.fr
Jean Potier
1Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 cedex 15, Marseille, France
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Ghislaine Caillol
1Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 cedex 15, Marseille, France
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Claire Debarnot
1Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 cedex 15, Marseille, France
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Fanny Rueda Boroni
1Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 cedex 15, Marseille, France
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Bénédicte Dargent
1Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 cedex 15, Marseille, France
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Abstract

The Axon Initial Segment [AIS], located within the first 30 μm of the axon, has two essential roles in generating action potentials and maintaining axonal identity. AIS assembly depends on a ßIV-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 ßIV-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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Posted November 06, 2015.
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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
bioRxiv 022962; doi: https://doi.org/10.1101/022962
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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
bioRxiv 022962; doi: https://doi.org/10.1101/022962

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