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Accueil > Bibliographie > The fibronectin type III-like domains of neurofascin-186 mediates gliomedin (...)

The fibronectin type III-like domains of neurofascin-186

J Biol Chem. 2011 Dec ;286(49):42426-34
The fibronectin type III-like domains of neurofascin-186 mediates gliomedin binding and its clustering at the developing nodes of ranvier.
Labasque M, Devaux JJ, Leveque C, Faivre-Sarrailh C.

The cell adhesion molecules of the immunoglobulin superfamily (Ig-CAMs) play a crucial role in the organization of the node of Ranvier in myelinated axons. In the PNS, Gliomedin (Gldn) secreted by Schwann cell microvilli binds NrCAM and NF186 and direct the nodal clustering of voltage-gated sodium channels (Nav). NF186 is the single axonal Gldn partner to ensure Nav clustering at nodes, whereas NrCAM is only required in glial cells (1). The olfactomedin domain of Gldn is implicated in the interaction with nodal Ig-CAMs. However, the interacting modules of NrCAM or NF186 involved in Gldn association are unknown. Here, we report that fibronectin type III-like (FnIII) domains of both Ig-CAMs mediate their interaction with Gldn in pull-down and cell binding assays. Using surface plasmon resonance assays, we determined that NrCAM and NF186 display similar affinity constant for their association with Gldn (Kd of 0.9 and 5.7 nM, respectively). We characterized the FnIII domains 1 and 2 of NF186 as interacting modules that ensure association with Gldn. We found that the soluble FnIII domains of NF186 (FnIII-Fc) bind on Schwann cells and inhibit Gldn and Nav clustering at heminodes, the precursors of mature nodes in myelinating cultures. Our study reveals the unexpected importance of FnIII domains of Ig-CAMs in the organization of nodes of Ranvier in peripheral axons. Thus, NF186 utilizes distinct modules to organize the multimeric nodal complex.


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