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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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EBP50/ERM localization in premyelinating/induced DRG explant cultures changes from cell surface microvilli to a focal concentration at the SC tip. After 6 d in vitro, cultures were stained for (A) EBP50 and (B) ERM. Note the numerous cell surface microvilli present on migrating SC. After 18 d, cultures were stained for (C) EBP50 and (D) neurofilament. Bipolar SCs displayed microvilli along their length. Matched standard cultures (d27) and cultures induced to myelinate with serum and ascorbate (d27/M6) were stained for (E and G) EBP50 and (F and H) neurofilament. There was discrete localization of EBP50 to SC tips in the induced cultures. (I–K) These EBP50-positive tips were also found with varying morphologies. Bars, 10 μm.
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fig2: EBP50/ERM localization in premyelinating/induced DRG explant cultures changes from cell surface microvilli to a focal concentration at the SC tip. After 6 d in vitro, cultures were stained for (A) EBP50 and (B) ERM. Note the numerous cell surface microvilli present on migrating SC. After 18 d, cultures were stained for (C) EBP50 and (D) neurofilament. Bipolar SCs displayed microvilli along their length. Matched standard cultures (d27) and cultures induced to myelinate with serum and ascorbate (d27/M6) were stained for (E and G) EBP50 and (F and H) neurofilament. There was discrete localization of EBP50 to SC tips in the induced cultures. (I–K) These EBP50-positive tips were also found with varying morphologies. Bars, 10 μm.

Mentions: The three ERM proteins (ezrin, radixin, and moesin) are present in SC microvilli (Melendez-Vasquez et al., 2001; Scherer et al., 2001). Hence, we used a pan-ERM antibody in conjunction with our EBP50 antibody to examine microvillar organization in developing SCs. After 6 d in vitro, EBP50 and ERM staining revealed numerous microvilli (Fig. 2, A and B) covering the surface of migrating SC precursors. Mature SCs, characterized by a bipolar phenotype (Jessen et al., 1994), also exhibited numerous microvilli decorating their length (Fig. 2 C).


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 in premyelinating/induced DRG explant cultures changes from cell surface microvilli to a focal concentration at the SC tip. After 6 d in vitro, cultures were stained for (A) EBP50 and (B) ERM. Note the numerous cell surface microvilli present on migrating SC. After 18 d, cultures were stained for (C) EBP50 and (D) neurofilament. Bipolar SCs displayed microvilli along their length. Matched standard cultures (d27) and cultures induced to myelinate with serum and ascorbate (d27/M6) were stained for (E and G) EBP50 and (F and H) neurofilament. There was discrete localization of EBP50 to SC tips in the induced cultures. (I–K) These EBP50-positive tips were also found with varying morphologies. Bars, 10 μm.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: EBP50/ERM localization in premyelinating/induced DRG explant cultures changes from cell surface microvilli to a focal concentration at the SC tip. After 6 d in vitro, cultures were stained for (A) EBP50 and (B) ERM. Note the numerous cell surface microvilli present on migrating SC. After 18 d, cultures were stained for (C) EBP50 and (D) neurofilament. Bipolar SCs displayed microvilli along their length. Matched standard cultures (d27) and cultures induced to myelinate with serum and ascorbate (d27/M6) were stained for (E and G) EBP50 and (F and H) neurofilament. There was discrete localization of EBP50 to SC tips in the induced cultures. (I–K) These EBP50-positive tips were also found with varying morphologies. Bars, 10 μm.
Mentions: The three ERM proteins (ezrin, radixin, and moesin) are present in SC microvilli (Melendez-Vasquez et al., 2001; Scherer et al., 2001). Hence, we used a pan-ERM antibody in conjunction with our EBP50 antibody to examine microvillar organization in developing SCs. After 6 d in vitro, EBP50 and ERM staining revealed numerous microvilli (Fig. 2, A and B) covering the surface of migrating SC precursors. Mature SCs, characterized by a bipolar phenotype (Jessen et al., 1994), also exhibited numerous microvilli decorating their length (Fig. 2 C).

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