F3/contactin, a neuronal cell adhesion molecule implicated in axogenesis and myelination

Abstract

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.

Cellular Form of Prion Protein Inhibits Reelin-Mediated Shedding of Caspr from the Neuronal Cell Surface to Potentiate Caspr-Mediated Inhibition of Neurite Outgrowth

“…While the cellular form of PrP has been linked to neurite outgrowth and neuronal survival (Graner et al, 2000;Zanata et al, 2002;Chen et al, 2003;Santuccione et al, 2005;Lima et al, 2007), the contactin-associated protein Caspr has not been directly linked to neurite outgrowth, although its direct interaction with contactin would suggest such a function, since this GPIlinked Ig superfamily adhesion molecule promotes axonal growth (Falk et al, 2002). Caspr also interacts with the receptorlike protein tyrosine phosphatase RTPT␤ , which induces neurite outgrowth by binding to contactin (Sakurai et al, 1997).…”

Truncated Prion Protein and Doppel Are Myelinotoxic in the Absence of Oligodendrocytic PrPC

“…Oligodendrocyte-restricted PrP C may repress in trans the axonal pathology elicited by mutant PrP. A cellular signal might be transduced through PrP C from oligodendrocytes to axons, analogously to other GPIanchored proteins (such as F3 and NCAM 120) that play a role in axon-myelin interactions (Falk et al, 2002). Because PrP C binds in vitro to the transmembrane and GPI-linked forms of NCAM (Schmitt-Ulms et al, 2001), it might contribute to the very same pathways.…”

“…If toxicity of ⌬PrP and Dpl results from interference with some PrP Cmediated signaling pathway and toxicity is counteracted by PrP C , these three proteins may compete for the same partners on rafts. Moreover, ⌬PrP and Dpl may disrupt normal axon-glia interaction and adhesion, whose integrity depends on GPIanchored and transmembrane proteins (Falk et al, 2002;Marcus et al, 2002;Bartsch, 2003;Vinson et al, 2003). To investigate the topology of ⌬PrP, we performed flotation assays on Optiprep gradients with cold Triton X-100-treated ⌬PrP o brain extracts.…”

Influence of Breaching the Connective Sheaths of the Donor Nerve on Its Myelinated Sensory Axons and on Their Sprouting into the End-to-Side Coapted Nerve in the Rat

“…39 In addition, it contains repulsive axon guidance cues, such as tenascin-C, and appears to contribute to axon fasciculation by preventing axons and Schwann cells from leaving the nerve bundle. 41,61 Its very function, therefore, makes the perineurium an unfavorable environment for supporting carry-through axonal sprouts, with possible exception at the sites where blood vessels cross the epineurium and perineurium. 62 As little morphological change of the perineurium was observed on both light and electron microscopy after non-injurious end-to-side coaptation, the invading Schwann cells were suggested to turn off repulsive signals for axonal extension into the perineurium.…”