Neuroglial Interactions at the Node of Ranvier
Action potentials in neurons are initiated at axon initial segments and propagated along axons through the activation of clusters of ion channels found at nodes of Ranvier. This project aims to determine the mechanisms underlying developmental assembly of these domains, the mechanisms that regulate their maintenance throughout life, and the consequences of nervous system diseases on these domains. We will use molecular, genetic, imaging, and biochemical methods to identify the complement and function of proteins involved in organizing and maintaining these domains in health and disease.
Relevance of the project to IDDRC mission:
Proper nervous system function requires the rapid, efficient, and faithful action potential generation at propagation. The development of nodes of Ranvier in myelinated axons depends on neuron-glia interactions. Thus, developmental disorders that result in failure to properly myelinate axons also fail to form proper nodes of Ranvier. Furthermore, many of the proteins found at axon initial segments (the site where the action potential is initiated and which shares a common molecular organization with the node of Ranvier) have been implicated in diverse developmental and neurological disorders including autism (mutant forms of Caspr2 – we recently described the molecular mechanism underlying assembly of Caspr2 containing protein complexes at the axon initial segment) and bipolar disorder (ankyrinG, the scaffolding protein shown to be essential for assembly and maintenance of axon initial segments and nodes of Ranvier has been shown to be a primary susceptibility gene for bipolar disorder).