Using super-resolution microscopy to map the molecular architecture of the axon

Orateur : Christophe LETERRIER (Université Aix-Marseille)

Neurons ensure the directed flow of information in the brain, thanks to their highly polarized architecture. The cell body and dendrites typically receive synaptic inputs and integrate them, whereas the axon initiates and propagates action potentials to presynaptic boutons that target downstream neurons. The intricate connectivity and molecular identity of axons must be robust over decades, but also must adapt to changes in neuronal activity and environment. The axon fulfill these seemingly opposite imperatives thanks to a compartmentalized architecture based on specific cytoskeletal and scaffold structures, ensuring the targeted transport and anchoring of axonal components. Thanks to the development of super-resolution microscopy, it is now possible to directly visualize molecular assemblies in situ down to a few nanometers, and to unravel how the cytoskeleton and scaffolds organize the movement of proteins along the axon. We have recently used STochastic Optical Reconstruction Microscopy (STORM) to map the nano-architecture of the axon initial segment, a key compartment for the maintenance of neuronal polarity. We found that the initial segment is highly organized, with a submembrane actin/spectrin lattice distributing membrane proteins along a periodic pattern, and the scaffolding protein ankyrin G protruding from this lattice toward the cytoplasm. In collaboration with the lab of Subhojit Roy (UCSD), we also recently identified new cytoskeletal structures in the axon. Using a combination of live-cell imaging and STORM nanoscopy, we characterized transient actin "trails" rapidly spurting from actin "hotspots" and are currently exploring their functions. This discovery suggests that there are more as yet uncharacterized cytoskeletal and scaffold structures important for axonal transport and presynaptic organization.

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