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Published online 8 September 2003. doi:10.1083/jcb.200305018
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© The Rockefeller University Press, 0021-9525/2003/9/1149 $5.00
The Journal of Cell Biology, Volume 162, Number 6, 1149-1160

Article

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

Sebastian Poliak1, Daniela Salomon1, Hadas Elhanany1, Helena Sabanay1, Brent Kiernan2, Larysa Pevny2, Colin L. Stewart3, Xiaorong Xu4, Shing-Yan Chiu5, Peter Shrager4, Andrew J.W. Furley2 and Elior Peles1

1 Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
2 Centre for Developmental Genetics, School of Medicine and Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK
3 Cancer and Developmental Biology Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702
4 Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, NY 14642
5 Department of Physiology, University of Wisconsin School of Medicine, Madison, WI 53706

Address correspondence to Dr. Elior Peles, Dept. of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel. Tel.: 972-8-934-2941. Fax: 972-8-934-4195. email: peles{at}weizmann.ac.il

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.

Key Words: axon; node of Ranvier; myelin; cell adhesion; Schwann cell

L. Pevny's present address is Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599-7250.

Abbreviations used in this paper: 4-AP, 4-aminopyridine; CNS, central nervous system; ES, embryonic stem; PNS, peripheral nervous system.


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