Limits...
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.

Show MeSH

Related in: MedlinePlus

Distribution of specific proteins in myelinated optic nerves of TAG-1 mutant mice. Localization of molecular components of nodes, paranodes, and juxtaparanodes in optic nerve sections of 2-mo-old (A, C, and E) wild-type (+/+) and (B, D, and F) TAG-1 mutant (−/−) mice. Sodium channels (red) and paranodin/Caspr (green) were normally clustered in the nodal and paranodal regions, respectively, in both (A) wild-type and (B) TAG-1–deficient mice. Caspr2-IR (green) was normally detected in the juxtaparanodal regions, in reference to the nodal sodium channels (red) in (C) wild-type animals, whereas it was not visible in (D) TAG-1 mutant mice. Kv1.1-IR was dramatically altered in mutant mice (F, arrows), as compared with wild-type animals (E, arrows). In TAG-1 mutant mice, Kv1.1 labeling was markedly decreased and was mostly restricted to a small area in contact with (F) paranodes. Bars: (A–F) 5 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172849&req=5

fig2: Distribution of specific proteins in myelinated optic nerves of TAG-1 mutant mice. Localization of molecular components of nodes, paranodes, and juxtaparanodes in optic nerve sections of 2-mo-old (A, C, and E) wild-type (+/+) and (B, D, and F) TAG-1 mutant (−/−) mice. Sodium channels (red) and paranodin/Caspr (green) were normally clustered in the nodal and paranodal regions, respectively, in both (A) wild-type and (B) TAG-1–deficient mice. Caspr2-IR (green) was normally detected in the juxtaparanodal regions, in reference to the nodal sodium channels (red) in (C) wild-type animals, whereas it was not visible in (D) TAG-1 mutant mice. Kv1.1-IR was dramatically altered in mutant mice (F, arrows), as compared with wild-type animals (E, arrows). In TAG-1 mutant mice, Kv1.1 labeling was markedly decreased and was mostly restricted to a small area in contact with (F) paranodes. Bars: (A–F) 5 μm.

Mentions: We examined whether the absence of TAG-1 altered axo–glial interactions at the molecular level by studying the localization of markers of nodal regions by immunofluorescence (IF) and laser confocal microscopy in optic nerve sections of wild-type and TAG-1–deficient mice. Double labeling for sodium channels and paranodin/Caspr in wild-type (Fig. 2 A) and mutant mice (Fig. 2 B) demonstrated normal clustering of these proteins in the nodal and paranodal regions, respectively, in both genotypes. We analyzed the organization of the juxtaparanodal regions of the TAG-1 mutant optic nerves by examining the expression of Caspr2 and Kv1.1 potassium channels subunits. As expected, in wild-type animals, Caspr2 was detected at juxtaparanodes in reference to the nodal sodium channels (Fig. 2 C), whereas in mutant mice, no enrichment of Caspr2 IR was detectable (Fig. 2 D). K+ channels distribution was also dramatically altered in mutant fibers because the overall staining for Kv1.1 was decreased and appeared to occupy much smaller areas than in wild-type animals (Fig. 2, E and F). Kv1.1-IR was detected only at the vicinity of paranodes in almost all the sites examined in the mutant optic nerves (Fig. 2 F, arrows). Similar alterations of Caspr2 and Kv1.1 channel distribution, contrasting with unchanged nodal and paranodal markers, were observed in spinal cord (unpublished data), indicating that TAG-1 plays a general role in the organization of axo–glial juxtaparanodal contacts in the CNS.


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 myelinated optic nerves of TAG-1 mutant mice. Localization of molecular components of nodes, paranodes, and juxtaparanodes in optic nerve sections of 2-mo-old (A, C, and E) wild-type (+/+) and (B, D, and F) TAG-1 mutant (−/−) mice. Sodium channels (red) and paranodin/Caspr (green) were normally clustered in the nodal and paranodal regions, respectively, in both (A) wild-type and (B) TAG-1–deficient mice. Caspr2-IR (green) was normally detected in the juxtaparanodal regions, in reference to the nodal sodium channels (red) in (C) wild-type animals, whereas it was not visible in (D) TAG-1 mutant mice. Kv1.1-IR was dramatically altered in mutant mice (F, arrows), as compared with wild-type animals (E, arrows). In TAG-1 mutant mice, Kv1.1 labeling was markedly decreased and was mostly restricted to a small area in contact with (F) paranodes. Bars: (A–F) 5 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172849&req=5

fig2: Distribution of specific proteins in myelinated optic nerves of TAG-1 mutant mice. Localization of molecular components of nodes, paranodes, and juxtaparanodes in optic nerve sections of 2-mo-old (A, C, and E) wild-type (+/+) and (B, D, and F) TAG-1 mutant (−/−) mice. Sodium channels (red) and paranodin/Caspr (green) were normally clustered in the nodal and paranodal regions, respectively, in both (A) wild-type and (B) TAG-1–deficient mice. Caspr2-IR (green) was normally detected in the juxtaparanodal regions, in reference to the nodal sodium channels (red) in (C) wild-type animals, whereas it was not visible in (D) TAG-1 mutant mice. Kv1.1-IR was dramatically altered in mutant mice (F, arrows), as compared with wild-type animals (E, arrows). In TAG-1 mutant mice, Kv1.1 labeling was markedly decreased and was mostly restricted to a small area in contact with (F) paranodes. Bars: (A–F) 5 μm.
Mentions: We examined whether the absence of TAG-1 altered axo–glial interactions at the molecular level by studying the localization of markers of nodal regions by immunofluorescence (IF) and laser confocal microscopy in optic nerve sections of wild-type and TAG-1–deficient mice. Double labeling for sodium channels and paranodin/Caspr in wild-type (Fig. 2 A) and mutant mice (Fig. 2 B) demonstrated normal clustering of these proteins in the nodal and paranodal regions, respectively, in both genotypes. We analyzed the organization of the juxtaparanodal regions of the TAG-1 mutant optic nerves by examining the expression of Caspr2 and Kv1.1 potassium channels subunits. As expected, in wild-type animals, Caspr2 was detected at juxtaparanodes in reference to the nodal sodium channels (Fig. 2 C), whereas in mutant mice, no enrichment of Caspr2 IR was detectable (Fig. 2 D). K+ channels distribution was also dramatically altered in mutant fibers because the overall staining for Kv1.1 was decreased and appeared to occupy much smaller areas than in wild-type animals (Fig. 2, E and F). Kv1.1-IR was detected only at the vicinity of paranodes in almost all the sites examined in the mutant optic nerves (Fig. 2 F, arrows). Similar alterations of Caspr2 and Kv1.1 channel distribution, contrasting with unchanged nodal and paranodal markers, were observed in spinal cord (unpublished data), indicating that TAG-1 plays a general role in the organization of axo–glial juxtaparanodal contacts in the CNS.

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