Nogo-A at CNS paranodes is a ligand of Caspr: Possible regulation of K + channel localization

Du Yu Nie, Zhi Hong Zhou, Beng Ti Ang, Felicia Y.H. Teng, Gang Xu, Tao Xiang, Chao Yang Wang, Li Zeng, Yasuo Takeda, Tian Le Xu, Yee Kong Ng, Catherine Faivre-Sarrailh, Brian Popko, Eng Ang Ling, Melitta Schachner, Kazutada Watanabe, Catherine J. Pallen*, Bor Luen Tang, Zhi Cheng Xiao

*Corresponding author for this work

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

We report Nogo-A as an oligodendroglial component congregating and interacting with the Caspr-F3 complex at paranodes. However, its receptor Nogo-66 receptor (NgR) does not segregate to specific axonal domains. CHO cells cotransfected with Caspr and F3, but not with F3 alone, bound specifically to substrates coated with Nogo-66 peptide and GST-Nogo-66. Binding persisted even after phosphatidylinositol-specific phospholipase C (PI-PLC) removal of GPI-linked F3 from the cell surface, suggesting a direct interaction between Nogo-66 and Caspr. Both Nogo-A and Caspr co-immunoprecipitated with Kv1.1 and Kv1.2, and the developmental expression pattern of both paralleled compared with Kv1.1, implicating a transient interaction between Nogo-A-Caspr and K + channels at early stages of myelination. In pathological models that display paranodal junctional defects (EAE rats, and Shiverer and CGT -/- mice), distances between the paired labeling of K+ channels were shortened significantly and their localization shifted toward paranodes, while paranodal Nogo-A congregation was markedly reduced. Our results demonstrate that Nogo-A interacts in trans with axonal Caspr at CNS paranodes, an interaction that may have a role in modulating axon-glial junction architecture and possibly K+-channel localization during development.

Original languageEnglish (US)
Pages (from-to)5666-5678
Number of pages13
JournalEMBO Journal
Volume22
Issue number21
DOIs
StatePublished - Nov 3 2003

Keywords

  • Caspr
  • K channel
  • Nogo-66 receptor
  • Nogo-A
  • Paranode

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Nie, D. Y., Zhou, Z. H., Ang, B. T., Teng, F. Y. H., Xu, G., Xiang, T., Wang, C. Y., Zeng, L., Takeda, Y., Xu, T. L., Ng, Y. K., Faivre-Sarrailh, C., Popko, B., Ling, E. A., Schachner, M., Watanabe, K., Pallen, C. J., Tang, B. L., & Xiao, Z. C. (2003). Nogo-A at CNS paranodes is a ligand of Caspr: Possible regulation of K + channel localization. EMBO Journal, 22(21), 5666-5678. https://doi.org/10.1093/emboj/cdg570