F3/contactin, a neuronal cell adhesion molecule implicated in axogenesis and myelination.
A general feature of the cell adhesion molecules belonging to the immunoglobulin family (Ig-CAMs) is to display a modular structure that provides a framework for multiple binding sites for other recognition molecules. Among this family, F3/contactin is a glycan phosphatidyl-inositol (GPI)-anchored molecule expressed by neurons that displays the distinctiveness to exert heterophilic but no homophilic binding activities. The Ig domains of F3/contactin were shown to interact with the L1 family of Ig-CAMs, including L1, NrCAM, and neurofascin. Binding between F3/contactin and NrCAM is known to modulate axonal elongation of the cerebellar granule cells and to control sensory axon guidance. F3/contactin mediates neuron-glial contacts through its association with extracellular matrix components (tenascin-R, tenascin-C) and RPTPbeta/phosphacan, influencing axonal growth and fasciculation. Another major role of F3/contactin is to organize axonal subdomains at the node of Ranvier of myelinated fibers in interplay with other Ig-CAMs, through its binding with caspr/paranodin at paranodes and the voltage-gated sodium channels in the nodal region. The F3/contactin deficient mice display a severe ataxia correlated with defects in axonal and dendritic projections in the cerebellum. These mice also display defects in nerve influx conduction due to the disruption of the axo-glial contacts at paranodes. Finally, the recent identification of a Drosophila homologue of F3/contactin indicated that this family of GPI-anchored CAMs plays a conserved function in axonal insulation.
Falk
Julien
J
Neurogenèse et Morphogenèse dans Développement et chez l'Adulte, UMR 6156, IBDM, Marseille, France.
Bonnon
Carine
C
Girault
Jean-Antoine
JA
Faivre-Sarrailh
Catherine
C
D000818:Animals; D001369:Axons / Q000737:chemistry / Q000648:ultrastructure*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology; D058966:Contactins; D006801:Humans; D009186:Myelin Sheath / Q000737:chemistry / Q000648:ultrastructure*; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure
D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins