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.
Traka
Maria
M
Department of Basic Science, University of Crete Medical School, Heraklion 71110, Crete, Greece.
Goutebroze
Laurence
L
Denisenko
Natalia
N
Bessa
Maria
M
Nifli
Artemisia
A
Havaki
Sophia
S
Iwakura
Yoichiro
Y
Fukamauchi
Fumihiko
F
Watanabe
Kazutada
K
Soliven
Betty
B
Girault
Jean-Antoine
JA
Karagogeos
Domna
D
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D019556:COS Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D058969:Contactin 2; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism* / Q000648:ultrastructure; D009431:Neural Conduction / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000648:ultrastructure; D051637:Shaker Superfamily of Potassium Channels
C548674:CNTN2 protein, human; C403049:CNTNAP2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1