MORPHOGENESIS OF THE NODE OF RANVIER - CO-CLUSTERS OF ANKYRIN AND ANKYRIN-BINDING INTEGRAL PROTEINS DEFINE EARLY DEVELOPMENTAL INTERMEDIATES

Ankyrin(G) 480/270 kDa and three ankyrin-binding integral membrane pro teins (neurofascin, NrCAM, and the voltage-dependent sodium channel) c olocalize within a specialized domain of the spectrin-actin network fo und at axonal segments of nodes of Ranvier in myelinated axons. Before myelination in embryonic nerves, ankyrin, 480/270 kDa and the related ankyrin isoform ankyrin, 440 kDa are cc-expressed along with NrCAM in an abundant, continuous distribution along the it. gth of axons. This study has resolved intermediate stages in the developmental transitio n from a continuous distribution of ankyrin, 480/270 kDa in ail axons to a highly polarized localization at the node of Ranvier in the devel oping rat sciatic nerve. The first detected event is formation of clus ters containing the cell adhesion molecules neurofascin and NrCAM at s ites independent of myelin-associated glycoprotein (MAG)-staining Schw ann cell processes. Subsequent steps involve recruitment of ankyrin, 4 80/270 kDa and the voltage-dependent sodium channel to cluster sites c ontaining cell adhesion molecules, and elaboration of MAG-staining Sch wann cell processes adjacent to these cluster sites. Formation of the mature node of Ranvier results from the fusion of asynchronously forme d pairs of clusters associated with MAG-positive Schwann cells flankin g the site of presumed node formation. Studies with the hypomyelinatin g mutant mouse trembler demonstrate that the elaboration of compact my elin is not required for the formation of these clustered nodal interm ediates. Clustering of neurofascin and NrCAM precedes redistribution o f ankyrin, 480/270 kDa and the voltage-dependent sodium channel, sugge sting that the adhesion molecules define the initial site for subseque nt assembly of ankyrin and the voltage-dependent sodium channel.