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Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers.

Traka M, Goutebroze L, Denisenko N, Bessa M, Nifli A, Havaki S, Iwakura Y, Fukamauchi F, Watanabe K, Soliven B, Girault JA, Karagogeos D - J. Cell Biol. (2003)

Bottom Line: Myelination results in a highly segregated distribution of axonal membrane proteins at nodes of Ranvier.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.This complex is analogous to that described previously at paranodes, suggesting that similar molecules are crucial for different types of axo-glial interactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Science, University of Crete Medical School, Heraklion 71110, Crete, Greece.

ABSTRACT
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.

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Distribution of specific proteins in sciatic nerves nodal regions of TAG-1 mutants and during development. (A–L) Localization of molecular components of nodes, paranodes, and juxtaparanodes in teased sciatic nerve fibers of 2-mo-old (A, C, E, G, I, and K) wild-type (+/+) and (B, D, F, H, J, and L) TAG-1 mutant (−/−) mice: (A and B) TAG-1 (red) and paranodin/Caspr (green); (C and D) NF155; (E and F) sodium channels; (G and H) MAG (green, paranodal regions, arrows; Schmidt-Lanterman incisures, arrowheads) and Caspr2 (red); (I and J) Kv1.1 potassium channels (green) and Caspr/paranodin (red); (K and L) Protein 4.1B (red) and Caspr/paranodin (green). Caspr2 and Kv1.1 labeling were dramatically altered in mutant mice, whereas the other markers appeared normal. Protein 4.1B-IR (red) was intense in the paranodal regions (arrows) where it was colocalized with Caspr/paranodin (green), and was also visible in the juxtaparanodal regions (arrowheads) of wild-type and mutant mice. Bars: (A–J) 20 μm and (K and L) 5 μm. (M and N) Distribution of Caspr2, TAG-1 and Kv1.2 in teased fibers of sciatic nerve of a P8 rat. (M) Caspr2 (red) and (N) TAG-1 (red) were detected in a limited number of fibers, where they appeared colocalized with (M and N) Kv1.2 potassium channels (green). Bar, 2.5 μm.
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fig4: Distribution of specific proteins in sciatic nerves nodal regions of TAG-1 mutants and during development. (A–L) Localization of molecular components of nodes, paranodes, and juxtaparanodes in teased sciatic nerve fibers of 2-mo-old (A, C, E, G, I, and K) wild-type (+/+) and (B, D, F, H, J, and L) TAG-1 mutant (−/−) mice: (A and B) TAG-1 (red) and paranodin/Caspr (green); (C and D) NF155; (E and F) sodium channels; (G and H) MAG (green, paranodal regions, arrows; Schmidt-Lanterman incisures, arrowheads) and Caspr2 (red); (I and J) Kv1.1 potassium channels (green) and Caspr/paranodin (red); (K and L) Protein 4.1B (red) and Caspr/paranodin (green). Caspr2 and Kv1.1 labeling were dramatically altered in mutant mice, whereas the other markers appeared normal. Protein 4.1B-IR (red) was intense in the paranodal regions (arrows) where it was colocalized with Caspr/paranodin (green), and was also visible in the juxtaparanodal regions (arrowheads) of wild-type and mutant mice. Bars: (A–J) 20 μm and (K and L) 5 μm. (M and N) Distribution of Caspr2, TAG-1 and Kv1.2 in teased fibers of sciatic nerve of a P8 rat. (M) Caspr2 (red) and (N) TAG-1 (red) were detected in a limited number of fibers, where they appeared colocalized with (M and N) Kv1.2 potassium channels (green). Bar, 2.5 μm.

Mentions: To determine whether TAG-1 was also critical for the molecular organization of peripheral nerve fibers, we examined the localization of markers of the nodal regions in sciatic nerves of TAG-1 knockout mice and wild-type littermates (Fig. 4). In wild-type animals, TAG-1-IR was enriched in juxtaparanodal regions, adjacent to paranodes, labeled with paranodin/Caspr (Fig. 4 A), as reported previously (Traka et al., 2002). In mutant mice, TAG-1-IR was absent, as expected, whereas paranodin/Caspr-IR appeared normal (Fig. 4 B). The glial protein NF155 was also properly localized at paranodes (Fig. 4, C and D) and sodium channels were normally restricted to the nodes in nerves of mice of both genotypes (Fig. 4, E and F). Myelin-associated glycoprotein (MAG) was normally enriched in paranodal regions, as well as at Schmidt-Lanterman incisures in wild-type and TAG-1 mutant mice (Fig. 4, G and H). Thus, in the absence of TAG-1, the major nodal and paranodal proteins were normally localized in sciatic nerves.


Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers.

Traka M, Goutebroze L, Denisenko N, Bessa M, Nifli A, Havaki S, Iwakura Y, Fukamauchi F, Watanabe K, Soliven B, Girault JA, Karagogeos D - J. Cell Biol. (2003)

Distribution of specific proteins in sciatic nerves nodal regions of TAG-1 mutants and during development. (A–L) Localization of molecular components of nodes, paranodes, and juxtaparanodes in teased sciatic nerve fibers of 2-mo-old (A, C, E, G, I, and K) wild-type (+/+) and (B, D, F, H, J, and L) TAG-1 mutant (−/−) mice: (A and B) TAG-1 (red) and paranodin/Caspr (green); (C and D) NF155; (E and F) sodium channels; (G and H) MAG (green, paranodal regions, arrows; Schmidt-Lanterman incisures, arrowheads) and Caspr2 (red); (I and J) Kv1.1 potassium channels (green) and Caspr/paranodin (red); (K and L) Protein 4.1B (red) and Caspr/paranodin (green). Caspr2 and Kv1.1 labeling were dramatically altered in mutant mice, whereas the other markers appeared normal. Protein 4.1B-IR (red) was intense in the paranodal regions (arrows) where it was colocalized with Caspr/paranodin (green), and was also visible in the juxtaparanodal regions (arrowheads) of wild-type and mutant mice. Bars: (A–J) 20 μm and (K and L) 5 μm. (M and N) Distribution of Caspr2, TAG-1 and Kv1.2 in teased fibers of sciatic nerve of a P8 rat. (M) Caspr2 (red) and (N) TAG-1 (red) were detected in a limited number of fibers, where they appeared colocalized with (M and N) Kv1.2 potassium channels (green). Bar, 2.5 μm.
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fig4: Distribution of specific proteins in sciatic nerves nodal regions of TAG-1 mutants and during development. (A–L) Localization of molecular components of nodes, paranodes, and juxtaparanodes in teased sciatic nerve fibers of 2-mo-old (A, C, E, G, I, and K) wild-type (+/+) and (B, D, F, H, J, and L) TAG-1 mutant (−/−) mice: (A and B) TAG-1 (red) and paranodin/Caspr (green); (C and D) NF155; (E and F) sodium channels; (G and H) MAG (green, paranodal regions, arrows; Schmidt-Lanterman incisures, arrowheads) and Caspr2 (red); (I and J) Kv1.1 potassium channels (green) and Caspr/paranodin (red); (K and L) Protein 4.1B (red) and Caspr/paranodin (green). Caspr2 and Kv1.1 labeling were dramatically altered in mutant mice, whereas the other markers appeared normal. Protein 4.1B-IR (red) was intense in the paranodal regions (arrows) where it was colocalized with Caspr/paranodin (green), and was also visible in the juxtaparanodal regions (arrowheads) of wild-type and mutant mice. Bars: (A–J) 20 μm and (K and L) 5 μm. (M and N) Distribution of Caspr2, TAG-1 and Kv1.2 in teased fibers of sciatic nerve of a P8 rat. (M) Caspr2 (red) and (N) TAG-1 (red) were detected in a limited number of fibers, where they appeared colocalized with (M and N) Kv1.2 potassium channels (green). Bar, 2.5 μm.
Mentions: To determine whether TAG-1 was also critical for the molecular organization of peripheral nerve fibers, we examined the localization of markers of the nodal regions in sciatic nerves of TAG-1 knockout mice and wild-type littermates (Fig. 4). In wild-type animals, TAG-1-IR was enriched in juxtaparanodal regions, adjacent to paranodes, labeled with paranodin/Caspr (Fig. 4 A), as reported previously (Traka et al., 2002). In mutant mice, TAG-1-IR was absent, as expected, whereas paranodin/Caspr-IR appeared normal (Fig. 4 B). The glial protein NF155 was also properly localized at paranodes (Fig. 4, C and D) and sodium channels were normally restricted to the nodes in nerves of mice of both genotypes (Fig. 4, E and F). Myelin-associated glycoprotein (MAG) was normally enriched in paranodal regions, as well as at Schmidt-Lanterman incisures in wild-type and TAG-1 mutant mice (Fig. 4, G and H). Thus, in the absence of TAG-1, the major nodal and paranodal proteins were normally localized in sciatic nerves.

Bottom Line: Myelination results in a highly segregated distribution of axonal membrane proteins at nodes of Ranvier.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.This complex is analogous to that described previously at paranodes, suggesting that similar molecules are crucial for different types of axo-glial interactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Science, University of Crete Medical School, Heraklion 71110, Crete, Greece.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus