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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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Ultrastructural organization of myelinated fibers and nerve function in TAG-1 mutant mice. (A–F) Ultrastructural organization of myelinated fibers. Myelin sheath thickness and compaction were similar in myelinated fibers of the ventral spinal cord region of 3-mo-old (A) wild-type and (B) TAG-1 mutant mice. The nodal (N), paranodal (P), and juxtaparanodal (J) regions appeared properly organized in longitudinal sections of wild-type (C) and mutant animals (D). In the paranodal region, the transverse bands (arrowheads) were normally present in both genotypes (E, wild type; F, mutant). Bars: (A and B) 0.1 μm; (C and D) 0.5 μm; and (E and F) 0.3 μm. (G and H) Electrophysiological studies of sciatic nerves. CMAPs and F waves were recorded after distal and proximal stimulation of sciatic nerves of 2-mo-old (G) wild-type and (H) TAG-1 mutant mice. There were no differences in the waveform, latencies and amplitudes of CMAPs between both genotypes.
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fig1: Ultrastructural organization of myelinated fibers and nerve function in TAG-1 mutant mice. (A–F) Ultrastructural organization of myelinated fibers. Myelin sheath thickness and compaction were similar in myelinated fibers of the ventral spinal cord region of 3-mo-old (A) wild-type and (B) TAG-1 mutant mice. The nodal (N), paranodal (P), and juxtaparanodal (J) regions appeared properly organized in longitudinal sections of wild-type (C) and mutant animals (D). In the paranodal region, the transverse bands (arrowheads) were normally present in both genotypes (E, wild type; F, mutant). Bars: (A and B) 0.1 μm; (C and D) 0.5 μm; and (E and F) 0.3 μm. (G and H) Electrophysiological studies of sciatic nerves. CMAPs and F waves were recorded after distal and proximal stimulation of sciatic nerves of 2-mo-old (G) wild-type and (H) TAG-1 mutant mice. There were no differences in the waveform, latencies and amplitudes of CMAPs between both genotypes.

Mentions: TAG-1–deficient mice survive and reproduce normally (Fukamauchi et al., 2001). Although mutant mice display a greater sensitivity to pro-convulsant stimuli and a marked elevation of adenosine A1 receptors in the hippocampus, morphological analysis of the cerebellum, spinal cord, and hippocampus of these mice did not reveal gross abnormalities (Fukamauchi et al., 2001). Because TAG-1 is also expressed in oligodendrocytes, we examined whether the absence of TAG-1 altered the ultrastructural organization of myelinated axons by electron microscopy. In ultrathin transverse spinal cord sections, myelin sheath thickness and compaction were similar in myelinated fibers of the ventral spinal cord region of wild-type (Fig. 1 A) and TAG-1 mutant mice (Fig. 1 B). The nodal, paranodal, and juxtaparanodal regions appeared properly organized in spinal cord sections of both wild-type (Fig. 1 C) and mutant animals (Fig. 1 D). Finally, the transverse bands, the hallmarks of normal axo–glial junctions, were normally present in both genotypes (Fig. 1, E and F, arrowheads). These results show that TAG-1 expression is not required for myelin sheath formation and structural organization of distinct axonal domains.


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)

Ultrastructural organization of myelinated fibers and nerve function in TAG-1 mutant mice. (A–F) Ultrastructural organization of myelinated fibers. Myelin sheath thickness and compaction were similar in myelinated fibers of the ventral spinal cord region of 3-mo-old (A) wild-type and (B) TAG-1 mutant mice. The nodal (N), paranodal (P), and juxtaparanodal (J) regions appeared properly organized in longitudinal sections of wild-type (C) and mutant animals (D). In the paranodal region, the transverse bands (arrowheads) were normally present in both genotypes (E, wild type; F, mutant). Bars: (A and B) 0.1 μm; (C and D) 0.5 μm; and (E and F) 0.3 μm. (G and H) Electrophysiological studies of sciatic nerves. CMAPs and F waves were recorded after distal and proximal stimulation of sciatic nerves of 2-mo-old (G) wild-type and (H) TAG-1 mutant mice. There were no differences in the waveform, latencies and amplitudes of CMAPs between both genotypes.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2172849&req=5

fig1: Ultrastructural organization of myelinated fibers and nerve function in TAG-1 mutant mice. (A–F) Ultrastructural organization of myelinated fibers. Myelin sheath thickness and compaction were similar in myelinated fibers of the ventral spinal cord region of 3-mo-old (A) wild-type and (B) TAG-1 mutant mice. The nodal (N), paranodal (P), and juxtaparanodal (J) regions appeared properly organized in longitudinal sections of wild-type (C) and mutant animals (D). In the paranodal region, the transverse bands (arrowheads) were normally present in both genotypes (E, wild type; F, mutant). Bars: (A and B) 0.1 μm; (C and D) 0.5 μm; and (E and F) 0.3 μm. (G and H) Electrophysiological studies of sciatic nerves. CMAPs and F waves were recorded after distal and proximal stimulation of sciatic nerves of 2-mo-old (G) wild-type and (H) TAG-1 mutant mice. There were no differences in the waveform, latencies and amplitudes of CMAPs between both genotypes.
Mentions: TAG-1–deficient mice survive and reproduce normally (Fukamauchi et al., 2001). Although mutant mice display a greater sensitivity to pro-convulsant stimuli and a marked elevation of adenosine A1 receptors in the hippocampus, morphological analysis of the cerebellum, spinal cord, and hippocampus of these mice did not reveal gross abnormalities (Fukamauchi et al., 2001). Because TAG-1 is also expressed in oligodendrocytes, we examined whether the absence of TAG-1 altered the ultrastructural organization of myelinated axons by electron microscopy. In ultrathin transverse spinal cord sections, myelin sheath thickness and compaction were similar in myelinated fibers of the ventral spinal cord region of wild-type (Fig. 1 A) and TAG-1 mutant mice (Fig. 1 B). The nodal, paranodal, and juxtaparanodal regions appeared properly organized in spinal cord sections of both wild-type (Fig. 1 C) and mutant animals (Fig. 1 D). Finally, the transverse bands, the hallmarks of normal axo–glial junctions, were normally present in both genotypes (Fig. 1, E and F, arrowheads). These results show that TAG-1 expression is not required for myelin sheath formation and structural organization of distinct axonal domains.

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