Subcortical cytoskeleton periodicity throughout the nervous system

Actin and its binding partner spectrin are among the most abundant proteins in many eukaryotic cells and are key components of the subcortical cytoskeleton. Their importance in the nervous system is reflected by the fact that actin represents 3–5% of the brain’s total protein content, with spectrin amounting to ~3% of the total membrane proteins1,2,3. Recently, fluorescence nanoscopy and new labeling strategies enabled the discovery of a ~190 nm periodic organization of the actin and spectrin subcortical cytoskeleton in axons and a subset of dendrites of hippocampal neurons4,5,6,7. Considering the high expression levels of both actin and spectrin throughout the nervous system, we speculated that the subcortical periodic organization might be a feature not only of excitatory hippocampal neurons, but also of other neuronal cell types and of non-neuronal cells. We therefore employed STimulated Emission Depletion (STED) nanoscopy of both fixed and living specimens. In this way we were able to identify a subcortical periodic lattice in the axons of other excitatory and inhibitory cultured neuronal cell types, and in highly specialized cells of the retina and, strikingly, in oligodendrocyte precursors. Finally, we analyzed actin organization at the nanoscale in intact nerve fibers, and found that actin and spectrin form a periodic structure even underneath the myelin coat. Our results suggest that this periodic organization is not an exclusive characteristic of hippocampal neurons but rather a general feature within the nervous system.