An Oligodendrocyte Cell Adhesion Molecule at the Site of Assembly of the Paranodal Axo-Glial Junction

Abstract

Two major isoforms of the cell adhesion molecule neurofascin NF186 and NF155 are expressed in the central nervous system (CNS). We have investigated their roles in the assembly of the node of Ranvier and show that they are targeted to distinct domains at the node. At the onset of myelination, NF186 is restricted to neurons, whereas NF155 localizes to oligodendrocytes, the myelin-forming glia of the CNS. Coincident with axon ensheathment, NF155 clusters at the paranodal regions of the myelin sheath where it localizes in apposition to the axonal adhesion molecule paranodin/contactin-associated protein (Caspr1), which is a constituent of the septate junction-like axo-glial adhesion zone. Immunoelectron microscopy confirmed that neurofascin is a glial component of the paranodal axo-glial junction. Concentration of NF155 with Caspr1 at the paranodal junctions of peripheral nerves is also a feature of Schwann cells. In Shiverer mutant mice, which assemble neither compact CNS myelin nor normal paranodes, NF155 (though largely retained at the cell body) is also distributed at ectopic sites along axons, where it colocalizes with Caspr1. Hence, NF155 is the first glial cell adhesion molecule to be identified in the paranodal axo-glial junction, where it likely interacts with axonal proteins in close association with Caspr1.

The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation

“…This theory is supported by studies that implicate ECM receptors and cell-cell adhesion molecules as key mediators of mechanotransduction (23). Interestingly, adhesion molecules have previously been shown to have a role in oligodendrocyte differentiation and myelination (24)(25)(26)(27)(28). ECM receptors such as integrins are also known to modulate the effects of extrinsic growth factors on various aspects of oligodendrocyte development (29,30).…”

Rafts in oligodendrocytes: Evidence and structure–function relationship

“…NF155 is localized within the paranodal loops where it interacts with the Caspr1 (contactin-associated protein, also known as paranodin)-F3/contactin protein complex on the axon (Charles et al, 2002;Tait et al, 2000), an interaction that is required for myelination in co-cultures of OLGs and neurons (Charles et al, 2002). The finding that NF155 is completely absent from paranodes of CGT (ceramide galactosyl transferase) knockout mice (Menon et al, 2003) indicates that raft assembly might be critical for the accumulation of NF155 in paranodes.…”

Heterophilic Interactions of Sodium Channel β1 Subunits with Axonal and Glial Cell Adhesion Molecules

“…Antimouse HA.11 was obtained from Covance Research Products, Inc. (Berkeley, CA). cDNA encoding Nf155 and anti-Nf155 antibodies were gifts from Dr. Peter Brophy (University of Edinburgh, Edinburgh, Scotland) (33). cDNAs encoding NrCAM and NrCAM-Fc (Nr-Fc) and antiNrCAM antibodies were provided by Dr. Martin Grumet (The State University of New Jersey, Piscataway, NJ) and were described previously (18).…”

“…Contactin is expressed at paranodes in the PNS, where it interacts with Caspr on the axonal membrane and neurofascin 155 (Nf155) on the Schwann cell membrane to form septatelike junctions that separate the nodal gap from the juxtaparanode (31)(32)(33). In the CNS, contactin is expressed in the nodal gap, where it interacts with sodium channels (17,32), as well as in the paranode.…”