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© The Rockefeller University Press, 0021-9525/2003/8/489 $5.00
The Journal of Cell Biology, Volume 162, Number 3, 489-498

Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient formation of nodes of Ranvier

Department of Cell Biology and Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01605

Address correspondence to Stephen Lambert, Dept. of Cell Biology, University of Massachusetts Medical School, 4 Biotech, 377 Plantation St., Suite 326, Worcester, MA 01605. Tel.: (508) 856-8665. Fax: (508) 856-8774. email: Stephen.Lambert{at}umassmed.edu

Nodes of Ranvier are specialized, highly polarized axonal domains crucial to the propagation of saltatory action potentials. In the peripheral nervous system, axo–glial cell contacts have been implicated in Schwann cell (SC) differentiation and formation of the nodes of Ranvier. SC microvilli establish axonal contact at mature nodes, and their components have been observed to localize early to sites of developing nodes. However, a role for these contacts in node formation remains controversial.

Using a myelinating explant culture system, we have observed that SCs reorganize and polarize microvillar components, such as the ezrin-binding phosphoprotein 50 kD/regulatory cofactor of the sodium-hydrogen exchanger isoform 3 (NHERF-1), actin, and the activated ezrin, radixin, and moesin family proteins before myelination in response to inductive signals. These components are targeted to the SC distal tips where live cell imaging reveals novel, dynamic growth cone–like behavior. Furthermore, localized activation of the Rho signaling pathway at SC tips gives rise to these microvillar component–enriched "caps" and influences the efficiency of node formation.

Key Words: glial cells; nodes of Ranvier; myelin sheath; growth cones; microvilli

Abbreviations used in this paper: BME, basal medium Eagle's; DRG, dorsal root ganglion; EBP50, ezrin-binding phosphoprotein 50 kD; ERM, ezrin, radixin, and moesin family proteins; LPA, lysophosphatidic acid; MAG, myelin-associated glycoprotein; MBP, myelin basic protein; ROCK, Rho-associated kinase; SC, Schwann cell; vgsc, voltage-gated sodium channel.

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