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

Gatto CL, Walker BJ, Lambert S - J. Cell Biol. (2003)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Program in Neuroscience, University of Massachusetts Medical School, 4 Biotech, 377 Plantation St., Suite 326, Worcester, MA 01605, USA.

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.

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Related in: MedlinePlus

EBP50/ERM localization to early and mature nodes in myelinating DRG explant cultures. (A, ST:d47; B, MY:d47/M26) Myelinated and comparable control cultures were stained for MBP to show mature myelin. (C–E) EBP50/AnkG/MBP revealed nodal specializations. (F) Note that SC microvillar EBP50 staining encompassed axonal AnkG. Less differentiated cultures (M5/6) were stained with EBP50 (I and L) and either βIV spectrin (H, axonal marker) or MAG (K, early myelin marker). (M and J) EBP50 was clearly present at early hemi- (arrowheads) and binary (arrows) nodes. Bars, 10 μm except where indicated.
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fig1: EBP50/ERM localization to early and mature nodes in myelinating DRG explant cultures. (A, ST:d47; B, MY:d47/M26) Myelinated and comparable control cultures were stained for MBP to show mature myelin. (C–E) EBP50/AnkG/MBP revealed nodal specializations. (F) Note that SC microvillar EBP50 staining encompassed axonal AnkG. Less differentiated cultures (M5/6) were stained with EBP50 (I and L) and either βIV spectrin (H, axonal marker) or MAG (K, early myelin marker). (M and J) EBP50 was clearly present at early hemi- (arrowheads) and binary (arrows) nodes. Bars, 10 μm except where indicated.

Mentions: Here, myelinating DRG explants were used to examine SC differentiation and formation of the nodes of Ranvier. This system allowed for the controlled induction of myelination upon the addition of serum and ascorbate to the culture media. This enabled the consistent generation of substantially myelinated cultures, as indicated by myelin basic protein (MBP) staining to reveal compacted myelin (Fig. 1 B). Occasionally, small numbers of segments were also observed in cultures maintained in standard feed (Fig. 1 A). When present, these segments were aberrantly short with irregular morphology and inconsistent nodal association.


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

Gatto CL, Walker BJ, Lambert S - J. Cell Biol. (2003)

EBP50/ERM localization to early and mature nodes in myelinating DRG explant cultures. (A, ST:d47; B, MY:d47/M26) Myelinated and comparable control cultures were stained for MBP to show mature myelin. (C–E) EBP50/AnkG/MBP revealed nodal specializations. (F) Note that SC microvillar EBP50 staining encompassed axonal AnkG. Less differentiated cultures (M5/6) were stained with EBP50 (I and L) and either βIV spectrin (H, axonal marker) or MAG (K, early myelin marker). (M and J) EBP50 was clearly present at early hemi- (arrowheads) and binary (arrows) nodes. Bars, 10 μm except where indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172691&req=5

fig1: EBP50/ERM localization to early and mature nodes in myelinating DRG explant cultures. (A, ST:d47; B, MY:d47/M26) Myelinated and comparable control cultures were stained for MBP to show mature myelin. (C–E) EBP50/AnkG/MBP revealed nodal specializations. (F) Note that SC microvillar EBP50 staining encompassed axonal AnkG. Less differentiated cultures (M5/6) were stained with EBP50 (I and L) and either βIV spectrin (H, axonal marker) or MAG (K, early myelin marker). (M and J) EBP50 was clearly present at early hemi- (arrowheads) and binary (arrows) nodes. Bars, 10 μm except where indicated.
Mentions: Here, myelinating DRG explants were used to examine SC differentiation and formation of the nodes of Ranvier. This system allowed for the controlled induction of myelination upon the addition of serum and ascorbate to the culture media. This enabled the consistent generation of substantially myelinated cultures, as indicated by myelin basic protein (MBP) staining to reveal compacted myelin (Fig. 1 B). Occasionally, small numbers of segments were also observed in cultures maintained in standard feed (Fig. 1 A). When present, these segments were aberrantly short with irregular morphology and inconsistent nodal association.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Program in Neuroscience, University of Massachusetts Medical School, 4 Biotech, 377 Plantation St., Suite 326, Worcester, MA 01605, USA.

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.

Show MeSH
Related in: MedlinePlus