Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers.
Myelination results in a highly segregated distribution of axonal membrane proteins at nodes of Ranvier. Here, we show the role in this process of TAG-1, a glycosyl-phosphatidyl-inositol-anchored cell adhesion molecule. In the absence of TAG-1, axonal Caspr2 did not accumulate at juxtaparanodes, and the normal enrichment of shaker-type K+ channels in these regions was severely disrupted, in the central and peripheral nervous systems. In contrast, the localization of protein 4.1B, an axoplasmic partner of Caspr2, was only moderately altered. TAG-1, which is expressed in both neurons and glia, was able to associate in cis with Caspr2 and in trans with itself. Thus, a tripartite intercellular protein complex, comprised of these two proteins, appears critical for axo-glial contacts at juxtaparanodes. This complex is analogous to that described previously at paranodes, suggesting that similar molecules are crucial for different types of axo-glial interactions.
Pubmed ID: 12975355 RIS Download
Animals | Brain | COS Cells | Cell Adhesion Molecules, Neuronal | Cell Communication | Cell Membrane | Contactin 2 | Cytoskeletal Proteins | Macromolecular Substances | Membrane Proteins | Mice | Mice, Knockout | Microscopy, Electron | Mutation | Nerve Fibers, Myelinated | Nerve Tissue Proteins | Nervous System | Neural Conduction | Neuroglia | Neuropeptides | Potassium Channels | Ranvier's Nodes | Shaker Superfamily of Potassium Channels