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Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1.

Poliak S, Salomon D, Elhanany H, Sabanay H, Kiernan B, Pevny L, Stewart CL, Xu X, Chiu SY, Shrager P, Furley AJ, Peles E - J. Cell Biol. (2003)

Bottom Line: In myelinated axons, K+ channels are concealed under the myelin sheath in the juxtaparanodal region, where they are associated with Caspr2, a member of the neurexin superfamily.Deletion of Caspr2 in mice by gene targeting revealed that it is required to maintain K+ channels at this location.These results demonstrate that Caspr2 and TAG-1 form a scaffold that is necessary to maintain K+ channels at the juxtaparanodal region, suggesting that axon-glia interactions mediated by these proteins allow myelinating glial cells to organize ion channels in the underlying axonal membrane.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.

ABSTRACT
In myelinated axons, K+ channels are concealed under the myelin sheath in the juxtaparanodal region, where they are associated with Caspr2, a member of the neurexin superfamily. Deletion of Caspr2 in mice by gene targeting revealed that it is required to maintain K+ channels at this location. Furthermore, we show that the localization of Caspr2 and clustering of K+ channels at the juxtaparanodal region depends on the presence of TAG-1, an immunoglobulin-like cell adhesion molecule that binds Caspr2. These results demonstrate that Caspr2 and TAG-1 form a scaffold that is necessary to maintain K+ channels at the juxtaparanodal region, suggesting that axon-glia interactions mediated by these proteins allow myelinating glial cells to organize ion channels in the underlying axonal membrane.

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Related in: MedlinePlus

Absence of TAG-1 at the juxtaparanode in Caspr2 PNS. Double-immunofluorescence staining of teased sciatic nerves isolated from wild-type (A–C) or Caspr2- mice (D–F), using antibodies to TAG-1 (green; A and D) and Na+ channels (red; B and E). Merge images are shown on the right of each row (C and F). Bar, 20 μm.
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fig5: Absence of TAG-1 at the juxtaparanode in Caspr2 PNS. Double-immunofluorescence staining of teased sciatic nerves isolated from wild-type (A–C) or Caspr2- mice (D–F), using antibodies to TAG-1 (green; A and D) and Na+ channels (red; B and E). Merge images are shown on the right of each row (C and F). Bar, 20 μm.

Mentions: A recent report demonstrated that TAG-1, a GPI-anchored cell adhesion molecule related to contactin, is expressed in Schwann cells and oligodendrocytes and is highly enriched in the juxtaparanodal region (Traka et al., 2002). To investigate the possible involvement of TAG-1 in Caspr2 function, we compared its expression along myelinated nerves in wild-type and Caspr2−/− mice. Staining of teased sciatic nerves of wild-type animals using a pAb to TAG-1 and an mAb to Na+ channels confirmed that TAG-1 was concentrated at the juxtaparanodal region (Fig. 5, A–C). In contrast, TAG-1 was barely detected or not detected at all in teased sciatic nerves of Caspr2−/− mutant (Fig. 5, D–F). Western blot analysis revealed that mutant nerves contained lower levels of TAG-1 compared with wild-type animals (unpublished data). Similarly, TAG-1 was absent from the juxtaparanodal region in optic nerve sections of Caspr2−/− mutant mice (unpublished data). Thus, we concluded that the accumulation of TAG-1 in the juxtaparanodes depends on the presence of Caspr2 in both PNS and the CNS.


Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1.

Poliak S, Salomon D, Elhanany H, Sabanay H, Kiernan B, Pevny L, Stewart CL, Xu X, Chiu SY, Shrager P, Furley AJ, Peles E - J. Cell Biol. (2003)

Absence of TAG-1 at the juxtaparanode in Caspr2 PNS. Double-immunofluorescence staining of teased sciatic nerves isolated from wild-type (A–C) or Caspr2- mice (D–F), using antibodies to TAG-1 (green; A and D) and Na+ channels (red; B and E). Merge images are shown on the right of each row (C and F). Bar, 20 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172860&req=5

fig5: Absence of TAG-1 at the juxtaparanode in Caspr2 PNS. Double-immunofluorescence staining of teased sciatic nerves isolated from wild-type (A–C) or Caspr2- mice (D–F), using antibodies to TAG-1 (green; A and D) and Na+ channels (red; B and E). Merge images are shown on the right of each row (C and F). Bar, 20 μm.
Mentions: A recent report demonstrated that TAG-1, a GPI-anchored cell adhesion molecule related to contactin, is expressed in Schwann cells and oligodendrocytes and is highly enriched in the juxtaparanodal region (Traka et al., 2002). To investigate the possible involvement of TAG-1 in Caspr2 function, we compared its expression along myelinated nerves in wild-type and Caspr2−/− mice. Staining of teased sciatic nerves of wild-type animals using a pAb to TAG-1 and an mAb to Na+ channels confirmed that TAG-1 was concentrated at the juxtaparanodal region (Fig. 5, A–C). In contrast, TAG-1 was barely detected or not detected at all in teased sciatic nerves of Caspr2−/− mutant (Fig. 5, D–F). Western blot analysis revealed that mutant nerves contained lower levels of TAG-1 compared with wild-type animals (unpublished data). Similarly, TAG-1 was absent from the juxtaparanodal region in optic nerve sections of Caspr2−/− mutant mice (unpublished data). Thus, we concluded that the accumulation of TAG-1 in the juxtaparanodes depends on the presence of Caspr2 in both PNS and the CNS.

Bottom Line: In myelinated axons, K+ channels are concealed under the myelin sheath in the juxtaparanodal region, where they are associated with Caspr2, a member of the neurexin superfamily.Deletion of Caspr2 in mice by gene targeting revealed that it is required to maintain K+ channels at this location.These results demonstrate that Caspr2 and TAG-1 form a scaffold that is necessary to maintain K+ channels at the juxtaparanodal region, suggesting that axon-glia interactions mediated by these proteins allow myelinating glial cells to organize ion channels in the underlying axonal membrane.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.

ABSTRACT
In myelinated axons, K+ channels are concealed under the myelin sheath in the juxtaparanodal region, where they are associated with Caspr2, a member of the neurexin superfamily. Deletion of Caspr2 in mice by gene targeting revealed that it is required to maintain K+ channels at this location. Furthermore, we show that the localization of Caspr2 and clustering of K+ channels at the juxtaparanodal region depends on the presence of TAG-1, an immunoglobulin-like cell adhesion molecule that binds Caspr2. These results demonstrate that Caspr2 and TAG-1 form a scaffold that is necessary to maintain K+ channels at the juxtaparanodal region, suggesting that axon-glia interactions mediated by these proteins allow myelinating glial cells to organize ion channels in the underlying axonal membrane.

Show MeSH
Related in: MedlinePlus