The axonal cytoskeleton at the nanoscale

Description

Abstract The intricate morphology and molecular identity of axons is maintained for decades, but also continuously adapts to changes in the environment and activity of neurons. Axons fulfill these paradoxical demands thanks to a unique cytoskeletal organization that ensures the coordinated transport, anchoring and mobility of axonal components (1). In our lab, we use super-resolution microscopy to map the nanoscale architecture actin-based structures within the axon. In the axon initial segment, a key compartment for the maintenance of neuronal polarity, we resolved a highly organized assembly encompassing the periodic actin/spectrin scaffold and its partners: ankyrin, myosins (2). We have also visualized new actin structures along the axon shaft: rings, hotspots and trails, and are now exploring their molecular organization and functions (3). For this, we develop a combination of versatile labeling, correlative live-cell/super-resolution/electron microscopy and quantitative analysis that allow for high-content, nanoscale interrogation of the axonal architecture (4).

1. Leterrier, C., Dubey, P., Roy, s. (2017). The nano-architecture of the axonal cytoskeleton. Nature Reviews Neurosciences 18(12), 713 – 726. 2. Leterrier, C., Potier, J., Caillol, G., Debarnot, C., Rueda-Boroni, F., Dargent, B. (2015). Nanoscale Architecture of the Axon Initial Segment Reveals an Organized and Robust Scaffold Cell Reports 13(12), 2781 – 2793. 3. Ganguly, A., Tang, Y., Wang, L., Ladt, K., Loi, J., Dargent, B., Leterrier, C., Roy, s. (2015). A dynamic formin-dependent deep F-actin network in axons. The Journal of Cell Biology 104(51), 20576 – 417. 4. Vassilopoulos, S., Gibaud, S., Jimenez, A., Caillol, G., Leterrier, C. (2019). Ultrastructure of the axonal periodic scaffold reveals a braid-like organization of actin rings. Nature Communications 10(1), 5803.