Nanoscale Architecture of the Axon Initial Segment Reveals an Organized and Robust Scaffold

作者：Leterrier Christophe^*; Potier Jean; Caillol Ghislaine; Debarnot Claire; Boroni Fanny Rueda; Dargent Benedicte

来源：Cell Reports, 2015, 13(12): 2781-2793.

DOI：10.1016/j.celrep.2015.11.051

The axon initial segment (AIS), located within the first 30 mu 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 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 beta IV-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 (similar to 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.

• 出版日期2015-12-29