Premium
Role of a Contactin multi‐molecular complex secreted by oligodendrocytes in nodal protein clustering in the CNS
Author(s) -
Dubessy AnneLaure,
Mazuir Elisa,
Rappeneau Quentin,
Ou Sokounthie,
Abi Ghanem Charly,
Piquand Kevin,
Aigrot MarieStéphane,
Thétiot Melina,
Desmazières Anne,
Chan Eric,
Fitzgibbon Matt,
Fleming Mark,
Krauss Raul,
Zalc Bernard,
Ranscht Barbara,
Lubetzki Catherine,
SolFoulon Nathalie
Publication year - 2019
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23681
Subject(s) - nodal , biology , oligodendrocyte , node of ranvier , hippocampal formation , sodium channel , neuroscience , myelin , microbiology and biotechnology , axon , central nervous system , anatomy , chemistry , organic chemistry , sodium
The fast and reliable propagation of action potentials along myelinated fibers relies on the clustering of voltage‐gated sodium channels at nodes of Ranvier. Axo‐glial communication is required for assembly of nodal proteins in the central nervous system, yet the underlying mechanisms remain poorly understood. Oligodendrocytes are known to support node of Ranvier assembly through paranodal junction formation. In addition, the formation of early nodal protein clusters (or prenodes) along axons prior to myelination has been reported, and can be induced by oligodendrocyte conditioned medium (OCM). Our recent work on cultured hippocampal neurons showed that OCM‐induced prenodes are associated with an increased conduction velocity (Freeman et al., 2015). We here unravel the nature of the oligodendroglial secreted factors. Mass spectrometry analysis of OCM identified several candidate proteins (i.e., Contactin‐1, ChL1, NrCAM, Noelin2, RPTP/Phosphacan, and Tenascin‐R). We show that Contactin‐1 combined with RPTP/Phosphacan or Tenascin‐R induces clusters of nodal proteins along hippocampal GABAergic axons. Furthermore, Contactin‐1‐immunodepleted OCM or OCM from Cntn1 ‐null mice display significantly reduced clustering activity, that is restored by addition of soluble Contactin‐1. Altogether, our results identify Contactin‐1 secreted by oligodendrocytes as a novel factor that may influence early steps of nodal sodium channel cluster formation along specific axon populations.