Stabilization of the cortical cytoskeleton by the lipid raft-associated protein cap23

In the present work, we identified the lipid raft-associated protein Cap23 to be involved in several important neuronal functions like the organization of lipid raft platforms, the maturation and stabilization of the actin- and intermediate filament cytoskeleton, and the formation of a scaffolding complex, which promotes mitochondrial docking. Cap23 was so far considered to play an important role in promoting axonal elongation during initial neurite outgrowth and especially during axonal regeneration. This protein was studied in mouse models of different genetic backgrounds or dorsal root ganglions in lesion experiments, which mainly focussed on anatomical alterations at the synapse or on the axonal regenerative response and concomitant changes in gene expression patterns. The findings in these studies demonstrated that Cap23 acts as an important intrinsic determinant of cytoskeletal regulation and growth-related processes in axons. Yet, the manner by which Cap23 could modulate these processes remained largely obscure. In the present work we took a closer look at diverse cell biological processes in cultured neurons, which bare the advantage that the development of single neurons and small networks can be easily studied at very high subcellular resolution using a combination of immunocytochemistry and live imaging. This approach thus enabled us to define cytoskeletal alterations caused by the absence of Cap23, besides providing a detailed study of mitochondrial trafficking in axons at high spatiotemporal resolution.