Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1.
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.
Poliak
Sebastian
S
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Salomon
Daniela
D
Elhanany
Hadas
H
Sabanay
Helena
H
Kiernan
Brent
B
Pevny
Larysa
L
Stewart
Colin L
CL
Xu
Xiaorong
X
Chiu
Shing-Yan
SY
Shrager
Peter
P
Furley
Andrew J W
AJ
Peles
Elior
E
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002450:Cell Communication / Q000235:genetics; D058969:Contactin 2; D018390:Gene Targeting; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D009431:Neural Conduction / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism / Q000648:ultrastructure; 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; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels