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Axonal spectrins: all-purpose fences.

Eshed-Eisenbach Y, Peles E - J. Cell Biol. (2013)

Bottom Line: A membrane barrier important for assembly of the nodes of Ranvier is found at the paranodal junction.This junction is comprised of axonal and glial adhesion molecules linked to the axonal actin-spectrin membrane cytoskeleton through specific adaptors.In this issue, Zhang et al. (2013.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.

ABSTRACT
A membrane barrier important for assembly of the nodes of Ranvier is found at the paranodal junction. This junction is comprised of axonal and glial adhesion molecules linked to the axonal actin-spectrin membrane cytoskeleton through specific adaptors. In this issue, Zhang et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201308116) show that axonal βII spectrin maintains the diffusion barrier at the paranodal junction. Thus, βII spectrin serves to compartmentalize the membrane of myelinated axons at specific locations that are determined either intrinsically (i.e., at the axonal initial segment), or by axoglial contacts (i.e., at the paranodal junction).

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βII spectrin helps organize membrane domains in myelinated axons. A schematic view depicting the organization of myelinated peripheral nerves around the nodes of Ranvier of wild type (WT, top), and mice mutants lacking axonal βII spectrin (middle) or the adhesion molecule Caspr (bottom). The presence of intact paranodal junction (PNJ) is marked by green vertical lines between the paranodal loops (PNL) and the axon. In wild-type nerves (top), both the paranodal junction and the cytoskeletal barrier are intact, resulting in the sequestering of Kv1 channels (blue) in the juxtaparanodal region (JXP) away from nodal sodium channels (red). In contrast to the paranodes in Caspr knockout that lack both the junction and the barrier function (bottom), in the βII spectrin mutant (middle) the barrier is compromised while the junction is intact. Note that the nodes in both mutants are wider compared to the wild type.
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fig1: βII spectrin helps organize membrane domains in myelinated axons. A schematic view depicting the organization of myelinated peripheral nerves around the nodes of Ranvier of wild type (WT, top), and mice mutants lacking axonal βII spectrin (middle) or the adhesion molecule Caspr (bottom). The presence of intact paranodal junction (PNJ) is marked by green vertical lines between the paranodal loops (PNL) and the axon. In wild-type nerves (top), both the paranodal junction and the cytoskeletal barrier are intact, resulting in the sequestering of Kv1 channels (blue) in the juxtaparanodal region (JXP) away from nodal sodium channels (red). In contrast to the paranodes in Caspr knockout that lack both the junction and the barrier function (bottom), in the βII spectrin mutant (middle) the barrier is compromised while the junction is intact. Note that the nodes in both mutants are wider compared to the wild type.

Mentions: Cell polarization is an essential feature that allows many cell types to fulfill their unique functions. Upon differentiation, polarized cells establish specialized membrane domains with distinct protein composition. In myelinated axons, such membrane compartmentalization is essential for fast and efficient propagation of action potentials in a saltatory manner. The membrane of these axons is divided into several distinct domains that include (1) the nodes of Ranvier, which are gaps between myelin segments where sodium channels are clustered; (2) the paranodal axoglial junction, where the terminal loops of the myelin attach to the axon; (3) the juxtaparanodal region, where Kv1 potassium channels are concentrated; and (4) the internode, which are covered by compact myelin (Fig. 1). In the peripheral nervous system (PNS), this intricate axonal organization requires specific intercellular contact sites between the axon and myelinating Schwann cells (Poliak and Peles, 2003; Eshed-Eisenbach and Peles, 2013), as well as the formation of membrane diffusion barriers that restrict the movement of proteins and lipids in the plasma membrane across different domains (Lasiecka et al., 2009; Katsuki et al., 2011).


Axonal spectrins: all-purpose fences.

Eshed-Eisenbach Y, Peles E - J. Cell Biol. (2013)

βII spectrin helps organize membrane domains in myelinated axons. A schematic view depicting the organization of myelinated peripheral nerves around the nodes of Ranvier of wild type (WT, top), and mice mutants lacking axonal βII spectrin (middle) or the adhesion molecule Caspr (bottom). The presence of intact paranodal junction (PNJ) is marked by green vertical lines between the paranodal loops (PNL) and the axon. In wild-type nerves (top), both the paranodal junction and the cytoskeletal barrier are intact, resulting in the sequestering of Kv1 channels (blue) in the juxtaparanodal region (JXP) away from nodal sodium channels (red). In contrast to the paranodes in Caspr knockout that lack both the junction and the barrier function (bottom), in the βII spectrin mutant (middle) the barrier is compromised while the junction is intact. Note that the nodes in both mutants are wider compared to the wild type.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3824006&req=5

fig1: βII spectrin helps organize membrane domains in myelinated axons. A schematic view depicting the organization of myelinated peripheral nerves around the nodes of Ranvier of wild type (WT, top), and mice mutants lacking axonal βII spectrin (middle) or the adhesion molecule Caspr (bottom). The presence of intact paranodal junction (PNJ) is marked by green vertical lines between the paranodal loops (PNL) and the axon. In wild-type nerves (top), both the paranodal junction and the cytoskeletal barrier are intact, resulting in the sequestering of Kv1 channels (blue) in the juxtaparanodal region (JXP) away from nodal sodium channels (red). In contrast to the paranodes in Caspr knockout that lack both the junction and the barrier function (bottom), in the βII spectrin mutant (middle) the barrier is compromised while the junction is intact. Note that the nodes in both mutants are wider compared to the wild type.
Mentions: Cell polarization is an essential feature that allows many cell types to fulfill their unique functions. Upon differentiation, polarized cells establish specialized membrane domains with distinct protein composition. In myelinated axons, such membrane compartmentalization is essential for fast and efficient propagation of action potentials in a saltatory manner. The membrane of these axons is divided into several distinct domains that include (1) the nodes of Ranvier, which are gaps between myelin segments where sodium channels are clustered; (2) the paranodal axoglial junction, where the terminal loops of the myelin attach to the axon; (3) the juxtaparanodal region, where Kv1 potassium channels are concentrated; and (4) the internode, which are covered by compact myelin (Fig. 1). In the peripheral nervous system (PNS), this intricate axonal organization requires specific intercellular contact sites between the axon and myelinating Schwann cells (Poliak and Peles, 2003; Eshed-Eisenbach and Peles, 2013), as well as the formation of membrane diffusion barriers that restrict the movement of proteins and lipids in the plasma membrane across different domains (Lasiecka et al., 2009; Katsuki et al., 2011).

Bottom Line: A membrane barrier important for assembly of the nodes of Ranvier is found at the paranodal junction.This junction is comprised of axonal and glial adhesion molecules linked to the axonal actin-spectrin membrane cytoskeleton through specific adaptors.In this issue, Zhang et al. (2013.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.

ABSTRACT
A membrane barrier important for assembly of the nodes of Ranvier is found at the paranodal junction. This junction is comprised of axonal and glial adhesion molecules linked to the axonal actin-spectrin membrane cytoskeleton through specific adaptors. In this issue, Zhang et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201308116) show that axonal βII spectrin maintains the diffusion barrier at the paranodal junction. Thus, βII spectrin serves to compartmentalize the membrane of myelinated axons at specific locations that are determined either intrinsically (i.e., at the axonal initial segment), or by axoglial contacts (i.e., at the paranodal junction).

Show MeSH
Related in: MedlinePlus