An alternative mechanism of early nodal clustering and myelination onset in GABAergic neurons of the central nervous system.

In vertebrates, fast saltatory conduction along myelinated axons relies on the node of Ranvier. How nodes assemble on CNS neurons is not yet fully understood. We previously described that node-like clusters can form prior to myelin deposition in hippocampal GABAergic neurons and are associated with increased conduction velocity. Here, we used a live imaging approach to characterize the intrinsic mechanisms underlying the assembly of these clusters prior to myelination. We first demonstrated that their components can partially preassemble prior to membrane targeting and determined the molecular motors involved in their trafficking. We then demonstrated the key role of the protein β2Nav for node-like clustering initiation. We further assessed the fate of these clusters when myelination proceeds. Our results shed light on the intrinsic mechanisms involved in node-like clustering prior to myelination and unravel a potential role of these clusters in node of Ranvier formation and in guiding myelination onset.