TY - JOUR T1 - Nanoscale architecture of the axon initial segment reveals an organized and robust scaffold JF - bioRxiv DO - 10.1101/022962 SP - 022962 AU - Christophe Leterrier AU - Jean Potier AU - Ghislaine Caillol AU - Claire Debarnot AU - Fanny Rueda Boroni AU - Bénédicte Dargent Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/11/06/022962.abstract N2 - 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. ER -