All About Multiple Sclerosis

More MS news articles for November 2003

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

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14592966&dopt=Abstract

EMBO J. 2003 Nov 3;22(21):5666-5678
Nie DY, Zhou ZH, Ang BT, Teng FY, Xu G, Xiang T, Wang CY, Zeng L, Takeda Y, Xu TL, Ng YK, Faivre-Sarrailh C, Popko B, Ling EA, Schachner M, Watanabe K, Pallen CJ, Tang BL, Xiao ZC.
Department of Clinical Research, Singapore General Hospital, Department of Anatomy, National University of Singapore, National Neuroscience Institute, Department of Biochemistry and Neurobiology Program, Office of Life Sciences, National University of Singapore, Institute of Molecular and Cell Biology, Singapore, Department of Anatomy, Sichuan University, Chengdu, School of Life Science, University of Science and Technology of China, Hefei, China, Department of Cell Recognition, Tokyo Metropolitan Institute of Gerontology, Tokyo, Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Japan, Neurobiologie de Interactions Cellulaires et Neuropathologie, FRE 2533, Institut Jean Roche, Marseilles, France, The Jack Miller Center for Peripheral Neuropathy, University of Chicago, Chicago, IL, USA, Zentrum fur Molekulare Neurobiologie, University of Hamburg, Hamburg, Germany and Department of Pediatrics, University of British Columbia, BC Research Institute for Children's and Women's Health, Vancouver, BC, Canada

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.