Cell biology of the neuron: Playing Lego at the nodes of Ranvier


NATURE REVIEWS | NEUROSCIENCE VOLUME 2 | JULY 2001 | 608 The assembly of neuronal specializations is sometimes reminiscent of building structures with Lego blocks: some pieces can attach only to specific partners, and there are blocks that you cannot position until others are already in place. A big challenge for the cell biologist is to discover the rules of neuronal Lego, which allow the formation of structures as complex as a growth cone or the postsynaptic density. The nodes of Ranvier — gaps in the myelin sheath that allow the efficient propagation of action potentials — are neuronal specializations that are less heralded, but also contain proteins galore: different subunits of voltage-gated sodium channels, cytoskeletal elements and components of the extracellular matrix. But how do the nodes assemble? A new piece of this puzzle has fallen into place after the publication of a recent study by Ratcliffe et al. in The Journal of Cell Biology. The extracellular domains of sodium channel β-subunits have an immunoglobulin-like domain, raising the possibility that β-subunits act as adhesion molecules. Ratcliffe et al. explored this idea by testing whether β-subunits interacted with neurofascin, an adhesion molecule that concentrates at prospective nodes of Ranvier. They found that the immunoglobulin-like domains of β1 and β3 subunits associated with neurofascin, and that this interaction did not involve their intracellular domains or their known association with the cytoskeletal protein ankyrin. Moreover, the association between β-subunits and neurofascin only occurred when the same cell expressed both molecules, indicating that this interaction does not mediate adhesion between neurons, but might be required for clustering heterologous molecules at specific membrane sites. These data contribute to a model in which neurofascin clusters at prospective nodes of Ranvier before engaging ankyrin, and both molecules then recruit β-subunits through intraand extracellular interactions. How are other proteins such as sodium channel α-subunits, tenascin R, NrCAM and spectrin then incorporated into the node? Many Lego blocks are left on the table. Juan Carlos López References and links ORIGINAL RESEARCH PAPER Ratcliffe, C. F. et al. Sodium channel β1 and β3 subunits associate with neurofascin through their extracellular immunoglobulin-like domain. J. Cell Biol. 154, 427–434 (2001) FURTHER READING Isom, L. L. & Catterall, W. A. Na+ channel subunits and Ig domains. Nature 383, 307–308 (1996) | Ratcliffe, C. F. et al. A sodium channel signaling complex: modulation by associated receptor protein tyrosine phosphatase β. Nature Neurosci. 3, 437–444 (2000) Playing Lego at the nodes of Ranvier C E L L B I O LO G Y O F T H E N E U R O N

DOI: 10.1038/35090006

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@article{Lpez2001CellBO, title={Cell biology of the neuron: Playing Lego at the nodes of Ranvier}, author={Juan Carlos L{\'o}pez}, journal={Nature Reviews Neuroscience}, year={2001}, volume={2}, pages={608-608} }