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 language | English (US) |
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Pages (from-to) | 5666-5678 |
Number of pages | 13 |
Journal | EMBO Journal |
Volume | 22 |
Issue number | 21 |
DOIs | |
State | Published - Nov 3 2003 |
All Science Journal Classification (ASJC) codes
- General Neuroscience
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology
Keywords
- Caspr
- K channel
- Nogo-66 receptor
- Nogo-A
- Paranode