Axo-glial interactions regulate the localization of axonal paranodal proteins

Mice incapable of synthesizing the abundant galactolipids of myelin exhibit disrupted paranodal axo-glial interactions in the central and peripheral n ervous systems. Using these mutants, we have analyzed the role that axo-gli al interactions play in the establishment of axonal protein distribution in the region of the node of Ranvier. Whereas the clustering of the nodal pro teins, sodium channels, ankyrin(G), and neurofascin was only slightly affec ted, the distribution of potassium channels and paranodin, proteins that ar e normally concentrated in the regions juxtaposed to the node, was dramatic ally altered, The potassium channels, which are normally concentrated in th e paranode/juxtaparanode, were not restricted to this region but were detec ted throughout the internode in the galactolipid-deficient mice. Paranodin/ contactin-associated protein (Caspr), a paranodal protein that is a potenti al neuronal mediator of axon-myelin binding, was not concentrated in the pa ranodal regions but was diffusely distributed along the internodal regions. Collectively, these findings suggest that the myelin galactolipids are ess ential for the proper formation of axo-glial interactions and demonstrate t hat a disruption in these interactions results in profound abnormalities in the molecular organization of the paranodal axolemma.