The generation, propagation, and modulation of electrical signals in the nervous system require the precise subcellular localization of ion channels in neurons. For example, disrupted ion channel or neurotransmitter receptor distribution or density play important roles in neuropathic pain, spinal cord injury, schizophrenia, myasthenia gravis, epilepsy, and multiple sclerosis. The three best examples of ion channel/receptor clustering in the nervous system are found at the synapse, the node of Ranvier, and the axon initial segment (AIS).
In the case of the synapse, the identification and characterization of synaptic protein components and complexes has led to remarkable advances in our understanding of synaptic physiology and function. We are even beginning to understand some of the rules that govern synaptic protein localization and retention. In contrast to the synapse and despite their central role in initiating, modulating, and transmitting electrical signals throughout the nervous system, very little is known about the mechanisms regulating localization and retention of proteins at the AIS and nodes of Ranvier.
Furthermore, very little is known about the consequences of nervous system injury on the maintenance and re-assembly of these critical domains.