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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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Model: SC progression toward myelination in DRG explant culture system. Highly motile, premyelinating SC migrate along axons extending from the DRG. These SC harbor numerous cell surface microvilli (red). Morphogenesis of the SC myelinating phenotype takes place with SCs becoming more longitudinally oriented and axon aligned while retaining many cell surface microvilli. Upon induction, typically using serum and ascorbate, Rho stimulation then leads to the formation of dynamic SC cap structures specifically enriched in activated ERM proteins and other microvillar components (red). Elaboration of the myelin membrane (blue) follows with the clustering of axonal components associated with the formation of early nodes (green).
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fig8: Model: SC progression toward myelination in DRG explant culture system. Highly motile, premyelinating SC migrate along axons extending from the DRG. These SC harbor numerous cell surface microvilli (red). Morphogenesis of the SC myelinating phenotype takes place with SCs becoming more longitudinally oriented and axon aligned while retaining many cell surface microvilli. Upon induction, typically using serum and ascorbate, Rho stimulation then leads to the formation of dynamic SC cap structures specifically enriched in activated ERM proteins and other microvillar components (red). Elaboration of the myelin membrane (blue) follows with the clustering of axonal components associated with the formation of early nodes (green).

Mentions: These observations are summarized in the model shown in Fig. 8. The initial stages of culture establishment include the migration of premyelinating SCs along the radially extended axons emanating from the DRG. These cells appear to be aggressively motile with numerous cell surface microvilli. As the cultures develop, SCs assume their characteristic bipolar myelinating phenotype with microvilli decorating their length. However, treatment of these cultures with serum and ascorbate (particularly serum) results in a reorganization of microvillar components into SC caps. Finally, SCs proceed to form myelin sheaths coupled with the clustering of proteins at the nodes of Ranvier.


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)

Model: SC progression toward myelination in DRG explant culture system. Highly motile, premyelinating SC migrate along axons extending from the DRG. These SC harbor numerous cell surface microvilli (red). Morphogenesis of the SC myelinating phenotype takes place with SCs becoming more longitudinally oriented and axon aligned while retaining many cell surface microvilli. Upon induction, typically using serum and ascorbate, Rho stimulation then leads to the formation of dynamic SC cap structures specifically enriched in activated ERM proteins and other microvillar components (red). Elaboration of the myelin membrane (blue) follows with the clustering of axonal components associated with the formation of early nodes (green).
© Copyright Policy
Related In: Results  -  Collection

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

fig8: Model: SC progression toward myelination in DRG explant culture system. Highly motile, premyelinating SC migrate along axons extending from the DRG. These SC harbor numerous cell surface microvilli (red). Morphogenesis of the SC myelinating phenotype takes place with SCs becoming more longitudinally oriented and axon aligned while retaining many cell surface microvilli. Upon induction, typically using serum and ascorbate, Rho stimulation then leads to the formation of dynamic SC cap structures specifically enriched in activated ERM proteins and other microvillar components (red). Elaboration of the myelin membrane (blue) follows with the clustering of axonal components associated with the formation of early nodes (green).
Mentions: These observations are summarized in the model shown in Fig. 8. The initial stages of culture establishment include the migration of premyelinating SCs along the radially extended axons emanating from the DRG. These cells appear to be aggressively motile with numerous cell surface microvilli. As the cultures develop, SCs assume their characteristic bipolar myelinating phenotype with microvilli decorating their length. However, treatment of these cultures with serum and ascorbate (particularly serum) results in a reorganization of microvillar components into SC caps. Finally, SCs proceed to form myelin sheaths coupled with the clustering of proteins at the nodes of Ranvier.

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