Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates.
AnkyrinG 480/270 kDa and three ankyrin-binding integral membrane proteins (neurofascin, NrCAM, and the voltage-dependent sodium channel) colocalize within a specialized domain of the spectrin-actin network found at axonal segments of nodes of Ranvier in myelinated axons. Before myelination in embryonic nerves, ankyrinG 480/270 kDa and the related ankyrin isoform ankyrinB 440 kDa are co-expressed along with NrCAM in an abundant, continuous distribution along the length of axons. This study has resolved intermediate stages in the developmental transition from a continuous distribution of ankyrinG 480/270 kDa in all axons to a highly polarized localization at the node of Ranvier in the developing rat sciatic nerve. The first detected event is formation of clusters containing the cell adhesion molecules neurofascin and NrCAM at sites independent of myelin-associated glycoprotein (MAG)-staining Schwann cell processes. Subsequent steps involve recruitment of ankyrinG 480/270 kDa and the voltage-dependent sodium channel to cluster sites containing cell adhesion molecules, and elaboration of MAG-staining Schwann cell processes adjacent to these cluster sites. Formation of the mature node of Ranvier results from the fusion of asynchronously formed pairs of clusters associated with MAG-positive Schwann cells flanking the site of presumed node formation. Studies with the hypomyelinating mutant mouse trembler demonstrate that the elaboration of compact myelin is not required for the formation of these clustered nodal intermediates. Clustering of neurofascin and NrCAM precedes redistribution of ankyrinG 480/270 kDa and the voltage-dependent sodium channel, suggesting that the adhesion molecules define the initial site for subsequent assembly of ankyrin and the voltage-dependent sodium channel.
Lambert
S
S
Department of Cell Biology and the Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Davis
J Q
JQ
Bennett
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V
D017398:Alternative Splicing; D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000906:Antibodies / Q000737:chemistry / Q000378:metabolism; D030161:Avian Proteins; D001369:Axons / Q000378:metabolism; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology / Q000378:metabolism*; D002645:Chickens; D046911:Macromolecular Substances; D051379:Mice; D008970:Molecular Weight; D009024:Morphogenesis; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009414:Nerve Growth Factors / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011901:Ranvier's Nodes / Q000378:metabolism*; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology / Q000196:embryology*; D015222:Sodium Channels / Q000276:immunology / Q000378:metabolism*; D013049:Spectrin / Q000378:metabolism
D017487:Ankyrins; D000906:Antibodies; D030161:Avian Proteins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D046911:Macromolecular Substances; D018992:Myelin-Associated Glycoprotein; C102222:NRCAM protein, Gallus gallus; D009414:Nerve Growth Factors; C504595:Nfasc protein, Gallus gallus; C504593:Nfasc protein, mouse; C504594:Nfasc protein, rat; C491151:Nrcam protein, mouse; D015222:Sodium Channels; D013049:Spectrin