RT Journal Article
SR Electronic
T1 Nanoscale architecture of the axon initial segment reveals an organized and robust scaffold
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 022962
DO 10.1101/022962
A1 Christophe Leterrier
A1 Jean Potier
A1 Ghislaine Caillol
A1 Claire Debarnot
A1 Fanny Rueda Boroni
A1 Bénédicte Dargent
YR 2015
UL http://biorxiv.org/content/early/2015/11/06/022962.abstract
AB 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.