Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization.
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.
Nie
Du-Yu
DY
Department of Clinical Research, Singapore General Hospital, Singapore.
Zhou
Zhi-Hong
ZH
Ang
Beng-Ti
BT
Teng
Felicia Y H
FY
Xu
Gang
G
Xiang
Tao
T
Wang
Chao-Yang
CY
Zeng
Li
L
Takeda
Yasuo
Y
Xu
Tian-Le
TL
Ng
Yee-Kong
YK
Faivre-Sarrailh
Catherine
C
Popko
Brian
B
Ling
Eng-Ang
EA
Schachner
Melitta
M
Watanabe
Kazutada
K
Pallen
Catherine J
CJ
Tang
Bor Luen
BL
Xiao
Zhi-Cheng
ZC
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D058966:Contactins; D006224:Cricetinae; D058851:GPI-Linked Proteins; D007150:Immunohistochemistry; D051662:Kv1.1 Potassium Channel; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D016253:Microscopy, Immunoelectron; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D009836:Oligodendroglia / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D014162:Transfection
D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; C105177:Cntnap1 protein, rat; D058966:Contactins; D058851:GPI-Linked Proteins; C496947:Kcna1 protein, mouse; D008024:Ligands; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; C419790:Rtn4r protein, mouse; C486581:Rtn4r protein, rat; D051662:Kv1.1 Potassium Channel