Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization.

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.

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@article{Nie2003NogoAAC, title={Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization.}, author={Du-yu Nie and Zhi-Hong Zhou and Beng-ti Ang and Felicia Yu Hsuan Teng and Gang Xu and Tao Xiang and Chao-Yang Wang and Li Zeng and Yasuo Takeda and Tian-le Xu and Y. K. Ng and Catherine Faivre-Sarrailh and Brian Popko and Eng-Ang Ling and Melitta Schachner and Kazutada Watanabe and Catherine J. Pallen and Bor Luen Tang and Zhi-cheng Xiao}, journal={The EMBO journal}, year={2003}, volume={22 21}, pages={5666-78} }