title: Nanoscale Architecture of the Axon Initial Segment Reveals an Organized and Robust Scaffold.
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 by using stochastic 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 amino terminus associates with the submembrane lattice, whereas the C terminus radially extends (∼ 32 nm on average) toward the cytosol. This AIS nano-architecture is highly resistant to cytoskeletal perturbations, indicating its role in structural stabilization. Our findings provide a comprehensive view of AIS molecular architecture and will help reveal the crucial physiological functions of this compartment.
authors.affiliation: Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 Cedex 15 Marseille, France. Electronic address: christophe.leterrier@univ-amu.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Leterrier
authors.affiliation: Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 Cedex 15 Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Potier
authors.affiliation: Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 Cedex 15 Marseille, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Caillol
authors.affiliation: Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 Cedex 15 Marseille, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Debarnot
authors.affiliation: Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 Cedex 15 Marseille, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Rueda Boroni
authors.affiliation: Aix Marseille Université, CNRS, CRN2M UMR7286, 13344 Cedex 15 Marseille, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dargent
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000502:physiology; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017487:Ankyrins
keywords: ankyrin G; axon initial segment; cytoskeleton; scaffold; super-resolution microscopy