Organization of myelinated axons

Rapid propagation of action potentials along myelinated axons depends on the high-density accumulation of voltage-gated sodium channels at regularly spaced interruptions in the myelin known as the nodes of Ranvier.  These nodal channels are separated by a specialized axoglial junction formed between the axon and myelinating glia from potassium channels that are concealed beneath the myelin sheath.  This organization, which depends on the presence of myelinating glial cells, is essential for the proper movement of the nerve impulses and its disruption results in the pathophysiological changes often seen in demyelinating human disorders.  One of the main research directions taken by our group is to understand how do myelinating glial cells control the organization of the axonal membrane they wrap? We have identified several cell adhesion molecules (Caspr, Caspr2, gliomedin and members of the Cadm family) that mediate axoglial contact and are required for the exquisite organization of the axonal membrane.  We are continuing to study their mechanism of action and are using different biochemical approaches to identify novel components of the nodes of Ranvier.  The latter is of particular interest as autoantibodies to some of the nodal proteins we identified are present in Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy.