Association of TAG-1 with Caspr2 Is Essential for the Molecular Organization of Juxtaparanodal Regions of Myelinated Fibers

• Published in: The Journal of cell biology Vol. 162; no. 6; pp. 1161 - 1172
• Main Authors: Traka, Maria, Goutebroze, Laurence, Denisenko, Natalia, Bessa, Maria, Nifli, Artemisia, Havaki, Sophia, Iwakura, Yoichiro, Fukamauchi, Fumihiko, Watanabe, Kazutada, Soliven, Betty, Girault, Jean-Antoine, Karagogeos, Domna
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 15.09.2003; The Rockefeller University Press
• Subjects: Animals; Antibodies; Brain - metabolism; Brain - ultrastructure; Cell Adhesion Molecules, Neuronal - deficiency; Cell Adhesion Molecules, Neuronal - genetics; Cell Communication - genetics; Cell Membrane - genetics; Cell Membrane - metabolism; Cell membranes; Cellular biology; Contactin 2; COS Cells; Cytoskeletal Proteins; Life Sciences; Macromolecular Substances; Membrane Proteins - metabolism; Mice; Mice, Knockout; Microscopy, Electron; Molecules; Mutation - genetics; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Myelinated - ultrastructure; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerves; Nervous system; Nervous System - metabolism; Nervous System - ultrastructure; Neural Conduction - genetics; Neurobiology; Neuroglia; Neuroglia - cytology; Neuroglia - metabolism; Neurons; Neurons and Cognition; Neuropeptides; Neuroscience; Potassium channels; Potassium Channels - genetics; Potassium Channels - metabolism; Proteins; Ranvier's Nodes - metabolism; Ranvier's Nodes - ultrastructure; Schwann cells; Shaker Superfamily of Potassium Channels
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200305078

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.