title: Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient formation of nodes of Ranvier.
abstract: 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.
authors.affiliation: Department of Cell Biology, Program in Neuroscience, University of Massachusetts Medical School, 4 Biotech, 377 Plantation St., Suite 326, Worcester, MA 01605, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Gatto
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Walker
authors.forename: Stephen
authors.initials: S
authors.lastname: Lambert
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D005333:Fetus; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D009924:Organ Culture Techniques; D017933:Peripheral Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000099149:Ezrin
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D020741:rho GTP-Binding Proteins; D000099149:Ezrin; C093376:sodium-hydrogen exchanger regulatory factor