Identifying how membrane proteins required for saltatory conduction are trafficked and stabilised in PNS axonal domains

Rapid nerve impulse conduction in vertebrate nerves depends on the clustering of voltage-gated sodium channels at nodes of Ranvier, which are gaps between the successive myelinated segments of axons. If nerves lose their myelin sheath, such as in multiple sclerosis or Charcot-Marie-Tooth disease, nodes are disrupted, leading to loss of nervous system function, blindness, paralysis or even death. Professor Brophy’s team have discovered that a protein called neurofascin plays an essential role in clustering these channel proteins at nodes in response to myelination, but there is currently little understanding of how it does this. The objective during this award is to directly visualise how neurofascin accomplishes this crucial task by using conventional and super-resolution light microscopy to track the targeting and fate of fluorescently-tagged nodal proteins in living nerves. This information will then be used to probe the mechanisms of node assembly and stabilisation.