Axo-Glial Septate Junctions

The L 1 subgroup of the immunoglobulin G superfamily participates in neurite outgrowth, neurite fasciculation and inter-neuronal adhesion. Almost all functional studies of the L 1 family have focused on their role in neurons. In this issue of the Journal of Cell Biology (Tait et al., 2000), the 155kD isoform of neurofascin, an ankyrin binding member of the L 1 family is identified as the first glial constituent of the paranodal axo-glial junction. As the major anchor between myelin and axons, these septate-like junctions are also thought to contain the molecular orchestrators for the polarization of axonal and myelin membranes into nodes of Ranvier. The importance of this polarization and how it may occur is the focus of this commentary. The sophisticated executive and motor functions we utilize to compete and survive depend upon rapid communication between billions of nerve cells. Rapid nerve communication can be achieved by increasing the diameter of the axons or cables that interconnect neurons to each other or to muscle and sensory endings. While this mechanism efficiently facilitates rapid nerve conduction in less sophisticated invertebrates, it would add unmanageable axonal bulk and brain mass to the mammalian CNS. Therefore, a mechanism for rapid nerve conduction evolved that concentrates the voltage-gated Na ϩ channels at discrete regions of the axon called nodes of Ranvier. The nodes are separated by a multilamellar, tightly com-pacted membrane called myelin that is synthesized by Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Myelin insulates axons and increases the resistance and decreases the capacitance of axonal membranes. The physiological end-product of myelination is saltatory conduction where the nerve impulse rapidly " jumps " from node to node. To obtain the same conductance without myelin, axonal diameters would have to increase 15,000-fold (Salzer, 1997). The clustering of Na ϩ channels at nodes requires the development of specialized domains of both axonal and my-elin surface membranes. It is unknown, however, whether nodal distributions are dictated by intrinsic axonal properties or by ensheathing glial cells. Myelination is required for axonal Na ϩ channel clustering in vivo (Ching et al., 1999; Rasband et al., 1999). This does not necessarily mean, however, that myelination or a glial component dictates the distribution of nodes of Ranvier. Internodal distances are not the same on all axons. Nodes are spaced at approximately 100 times the diameter of the mature axon and …