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Membrane molecule keeps nerve impulses hopping
Date:1/26/2011

ot been clearly defined in a mammalian system, they decided to study the function of this protein in laboratory mice.

Using targeted gene deletion methods, the UNC scientists genetically engineered mice lacking Neurofascin 186 in their neurons. "This caused the failure of sodium channels and Ankyrin-G to accumulate at the nodes of Ranvier. The result was paralysis, as there was no nerve impulse conductance," Bhat said.

According to Bhat, Neurofascin is an adhesion molecule that serves as the nodal organizer. "Its job is to cluster at the nodes of Ranvier. In doing so, it brings together sodium channels and Ankyrin-G where they interact to form the nodal complex. And if you don't have this protein, the node is compromised and there is no impulse propagation along the axon."

In further analysis, the researchers identified another important function of the nodes of Ranvier in myelinated nerve cells: to act as barriers to prevent the invasion of the nodal gap by neighboring paranodal molecular complexes. "So this tells us that sodium channels, Neurofascin 186, and Ankyrin-G must always remain in the node to have functional organization. If they don't, the flanking paranodes will move in and occupy the nodal gap and block nerve conduction," Bhat said.

The UNC neuroscientists see clinical implications for human disease. "In MS, for example, the proteins that make up the nodal complex start diffusing out from their normal location once you start losing the myelin sheath. If we can restore the nodal complex in nerve fibers, we may be able to restore some nerve conduction and function in affected axons." Their future studies are aimed at understanding whether the nodal complex could be reorganized and nerve conduction restored in genetically modified mutant mice.

"The discovery of an essential gap protein is exciting because it opens up the possibility that tweaking the protein could restore normal gap function in people with mu
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Contact: Les Lang
llang@med.unc.edu
919-966-9366
University of North Carolina School of Medicine
Source:Eurekalert  

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