Neuronal cell adhesion molecules and cytotactin are colocalized at the node of Ranvier.

Abstract

Abstract. Immunocytochemical methods were used toshow that Ng-CAM (the neuron-glia cell adhesion molecule), N-CAM (the neural cell adhesion molecule), and the extracellular matrix protein cytotactin are highly concentrated at nodes of Ranvier of the adult chicken and mouse. In contrast, unmyelinated axonal fibers were uniformly stained by specific antibodies to both CAMs but not by antibodies to cytotactin. Ultrastructural immunogold techniques indicated that both N-CAM and Ng-CAM were enriched in the nodal axoplasm and axolemma of myelinated fibers as well as within the nodal regions of the myelinating Schwann cell. At embryonic day 14, before myelination had occurred, small-caliber fibers of chick embryos showed periodic coincident accumulations of the two CAMs but not of cytotactin, with faint labeling in the axonal regions between accumulations. Cytotactin was found on Schwann cells and in connective tissue. By embryonic day 18, nodal accumulations of CAMs were first observed in a few medium-and large-caliber fibers. Immunoblot analyses indicated that embryonic to adult conversion of N-CAM and a progressive decrease in the amount of Ng-CAM and N-CAM occurred while nodes were forming. Sciatic nerves of mouse mutants with defects in cell interactions showed abnormalities in the distribution patterns and amount of Ng-CAM, N-CAM, and cytotactin that were consistent with the known morphological nodal disorders. In trembler (+/Tr), intense staining for both CAMs appeared all along the fibers and the amounts of N-CAM in the sciatic nerve were found to be increased. In mice with motor endplate disease (med/med), Ng-CAM and N-CAM, but not cytotactin, were localized in the widened nodes. Both trembler and med/med Schwann cells stained intensely for cytotactin, in contrast to normal Schwann cells which stained only slightly. All of these findings are consistent with the hypothesis that surface modulation of neuronal CAMs mediated by signals shared between neurons and glia may be necessary for establishing and maintaining the nodes of Ranvier.

Mechanisms and Roles of Axon-Schwann Cell Interactions

“…Three ERM proteins ezrin, radixin, and moesin, as well as ezrin-binding protein EBP50 and Rho-A GTPase, are localized at the microvilli (Melendez-Vasquez et al, 2001;Scherer et al, 2001). Several extracellular matrix proteins are present in the nodal gap under the basal lamina, including the hyaluronan-binding proteoglycan versican (Apostolski et al, 1994), tenascin C (Rieger et al, 1986;Martini et al, 1990), and syndecans . Dystroglycan is also located at the nodes (Saito et al, 2003).…”

The Clustering of Axonal Sodium Channels during Development of the Peripheral Nervous System

“…For example, several studies show that adhesion molecules of the immunoglobulin superfamily are important for Schwann cell ensheathment of axons (Seilheimer et al, 1989;Fruttiger et al, 1995). Furthermore, the expression of various surface glycoproteins by glia and axons is dependent on developmental state (Martini and Schachner, 1986;Rieger et al, 1986;Nolte et al, 1989;Shatz, 1990).…”

Expression of GlN1-Immunoreactive Glycoproteins during Development and Regeneration in Avian Peripheral Nerve

“…It has been found in the chick on Schwann cells [7] and in connective tissue at E14 [57], and in the perineurium and along endoneurial tubes of nerve fasci cles of transected or crushed nerve [7]. Cyto tactin in myelinated nerve fibers was con centrated at the node of Ranvier, while cytotactin staining was weak or absent in unmyelinated fibers [59]. The cytotactincontaining fraction, purified by HNK-1 immunoaffinity chromatography from a deter gent extract of E14 chicken brain, is composed of three molecules with Mr of 220, 200, and 190 kD [50,57].…”

“…The cytotactincontaining fraction, purified by HNK-1 immunoaffinity chromatography from a deter gent extract of E14 chicken brain, is composed of three molecules with Mr of 220, 200, and 190 kD [50,57]. Cytotactin appears to function in intercellular and cell-substra tum interactions [59,60], and, like N-CAM and Ng-CAM [6], has been studied after nerve transection [7]. The peak intensity of cytotactin in regenerating peripheral nerve occurred from 10 to 20 days following axotomy, and, in the proximal stump, was found to surround axons; in the distal stump cytotactin staining was localized in Schwann cell cytoplasm [7], The temporal appearance of cytotactin after axotomy correlates well with the presence of the high molecular weight GIN 1-reactive proteins in the distal stump.…”