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Axo-glial interactions regulate the localization of axonal paranodal proteins.

Dupree JL, Girault JA, Popko B - J. Cell Biol. (1999)

Bottom Line: Using these mutants, we have analyzed the role that axo-glial interactions play in the establishment of axonal protein distribution in the region of the node of Ranvier.Whereas the clustering of the nodal proteins, sodium channels, ankyrin(G), and neurofascin was only slightly affected, the distribution of potassium channels and paranodin, proteins that are normally concentrated in the regions juxtaposed to the node, was dramatically altered.Paranodin/contactin-associated protein (Caspr), a paranodal protein that is a potential neuronal mediator of axon-myelin binding, was not concentrated in the paranodal regions but was diffusely distributed along the internodal regions.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

ABSTRACT
Mice incapable of synthesizing the abundant galactolipids of myelin exhibit disrupted paranodal axo-glial interactions in the central and peripheral nervous systems. Using these mutants, we have analyzed the role that axo-glial interactions play in the establishment of axonal protein distribution in the region of the node of Ranvier. Whereas the clustering of the nodal proteins, sodium channels, ankyrin(G), and neurofascin was only slightly affected, the distribution of potassium channels and paranodin, proteins that are normally concentrated in the regions juxtaposed to the node, was dramatically altered. The potassium channels, which are normally concentrated in the paranode/juxtaparanode, were not restricted to this region but were detected throughout the internode in the galactolipid-defi- cient mice. Paranodin/contactin-associated protein (Caspr), a paranodal protein that is a potential neuronal mediator of axon-myelin binding, was not concentrated in the paranodal regions but was diffusely distributed along the internodal regions. Collectively, these findings suggest that the myelin galactolipids are essential for the proper formation of axo-glial interactions and demonstrate that a disruption in these interactions results in profound abnormalities in the molecular organization of the paranodal axolemma.

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(a) In the spinal cord of wild-type mice, potassium channels (red) are concentrated in the juxtaparanodes, and to a lesser extent, in the paranode, whereas the sodium channels (green) are restricted to the nodes of Ranvier. (b) In contrast, the potassium channels rarely accumulate in the juxtaparanodes of spinal cord tissue from the galactolipid-deficient mice. However, similar to the wild-type, the sodium channels cluster in the nodes but the sodium channel domains are slightly longer in the mutant as compared with the wild-type. The distribution of the potassium and sodium channels in the PNS is similar to the CNS for both the wild-type (c) and the mutant (d) mice. Note that in the CNS and the PNS of the galactolipid-deficient mice the channel domains occasionally overlap (yellow). a and b were generated as the compilation of eight consecutive images each 0.4 μm apart. c and d were generated as the compilation of 10 images each 0.26 μm apart. Bar, 5 μm.
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Figure 1: (a) In the spinal cord of wild-type mice, potassium channels (red) are concentrated in the juxtaparanodes, and to a lesser extent, in the paranode, whereas the sodium channels (green) are restricted to the nodes of Ranvier. (b) In contrast, the potassium channels rarely accumulate in the juxtaparanodes of spinal cord tissue from the galactolipid-deficient mice. However, similar to the wild-type, the sodium channels cluster in the nodes but the sodium channel domains are slightly longer in the mutant as compared with the wild-type. The distribution of the potassium and sodium channels in the PNS is similar to the CNS for both the wild-type (c) and the mutant (d) mice. Note that in the CNS and the PNS of the galactolipid-deficient mice the channel domains occasionally overlap (yellow). a and b were generated as the compilation of eight consecutive images each 0.4 μm apart. c and d were generated as the compilation of 10 images each 0.26 μm apart. Bar, 5 μm.

Mentions: To better understand the consequences that altered axo-glial interactions of the CNS (Dupree et al. 1998) and PNS (Dupree and Popko 1999) have on the establishment of ion channel domains, we analyzed the distribution of the nodally clustered voltage-gated sodium channels and the paranodal/juxtaparanodal Kv1.1 potassium channels in the CGT-deficient mice. In both the mutant and wild-type mice, CNS and PNS sodium channels were concentrated in small regions that were presumptive nodes of Ranvier (Fig. 1). Similar results have been reported previously regarding sodium channel distribution in the PNS of galactolipid-deficient mice (Bosio et al. 1998). Since we reported previously that CNS nodal length is increased in the galactolipid-deficient mice (Dupree et al. 1998), we measured the length and the width of the sodium channel domain and report node length as a function of axon caliber. In the CNS, the length to width ratio was significantly greater in the mutant (1.17 ± 0.05; n = 3 mice and 36 nodes; P < 0.02 by t test) compared with littermate wild-type (0.75 ± 0.13; n = 3 mice and 35 nodes) mice, indicating that the sodium channel domains, which likely corresponds to nodal length, were increased in the galactolipid-deficient animals.


Axo-glial interactions regulate the localization of axonal paranodal proteins.

Dupree JL, Girault JA, Popko B - J. Cell Biol. (1999)

(a) In the spinal cord of wild-type mice, potassium channels (red) are concentrated in the juxtaparanodes, and to a lesser extent, in the paranode, whereas the sodium channels (green) are restricted to the nodes of Ranvier. (b) In contrast, the potassium channels rarely accumulate in the juxtaparanodes of spinal cord tissue from the galactolipid-deficient mice. However, similar to the wild-type, the sodium channels cluster in the nodes but the sodium channel domains are slightly longer in the mutant as compared with the wild-type. The distribution of the potassium and sodium channels in the PNS is similar to the CNS for both the wild-type (c) and the mutant (d) mice. Note that in the CNS and the PNS of the galactolipid-deficient mice the channel domains occasionally overlap (yellow). a and b were generated as the compilation of eight consecutive images each 0.4 μm apart. c and d were generated as the compilation of 10 images each 0.26 μm apart. Bar, 5 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2168103&req=5

Figure 1: (a) In the spinal cord of wild-type mice, potassium channels (red) are concentrated in the juxtaparanodes, and to a lesser extent, in the paranode, whereas the sodium channels (green) are restricted to the nodes of Ranvier. (b) In contrast, the potassium channels rarely accumulate in the juxtaparanodes of spinal cord tissue from the galactolipid-deficient mice. However, similar to the wild-type, the sodium channels cluster in the nodes but the sodium channel domains are slightly longer in the mutant as compared with the wild-type. The distribution of the potassium and sodium channels in the PNS is similar to the CNS for both the wild-type (c) and the mutant (d) mice. Note that in the CNS and the PNS of the galactolipid-deficient mice the channel domains occasionally overlap (yellow). a and b were generated as the compilation of eight consecutive images each 0.4 μm apart. c and d were generated as the compilation of 10 images each 0.26 μm apart. Bar, 5 μm.
Mentions: To better understand the consequences that altered axo-glial interactions of the CNS (Dupree et al. 1998) and PNS (Dupree and Popko 1999) have on the establishment of ion channel domains, we analyzed the distribution of the nodally clustered voltage-gated sodium channels and the paranodal/juxtaparanodal Kv1.1 potassium channels in the CGT-deficient mice. In both the mutant and wild-type mice, CNS and PNS sodium channels were concentrated in small regions that were presumptive nodes of Ranvier (Fig. 1). Similar results have been reported previously regarding sodium channel distribution in the PNS of galactolipid-deficient mice (Bosio et al. 1998). Since we reported previously that CNS nodal length is increased in the galactolipid-deficient mice (Dupree et al. 1998), we measured the length and the width of the sodium channel domain and report node length as a function of axon caliber. In the CNS, the length to width ratio was significantly greater in the mutant (1.17 ± 0.05; n = 3 mice and 36 nodes; P < 0.02 by t test) compared with littermate wild-type (0.75 ± 0.13; n = 3 mice and 35 nodes) mice, indicating that the sodium channel domains, which likely corresponds to nodal length, were increased in the galactolipid-deficient animals.

Bottom Line: Using these mutants, we have analyzed the role that axo-glial interactions play in the establishment of axonal protein distribution in the region of the node of Ranvier.Whereas the clustering of the nodal proteins, sodium channels, ankyrin(G), and neurofascin was only slightly affected, the distribution of potassium channels and paranodin, proteins that are normally concentrated in the regions juxtaposed to the node, was dramatically altered.Paranodin/contactin-associated protein (Caspr), a paranodal protein that is a potential neuronal mediator of axon-myelin binding, was not concentrated in the paranodal regions but was diffusely distributed along the internodal regions.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

ABSTRACT
Mice incapable of synthesizing the abundant galactolipids of myelin exhibit disrupted paranodal axo-glial interactions in the central and peripheral nervous systems. Using these mutants, we have analyzed the role that axo-glial interactions play in the establishment of axonal protein distribution in the region of the node of Ranvier. Whereas the clustering of the nodal proteins, sodium channels, ankyrin(G), and neurofascin was only slightly affected, the distribution of potassium channels and paranodin, proteins that are normally concentrated in the regions juxtaposed to the node, was dramatically altered. The potassium channels, which are normally concentrated in the paranode/juxtaparanode, were not restricted to this region but were detected throughout the internode in the galactolipid-defi- cient mice. Paranodin/contactin-associated protein (Caspr), a paranodal protein that is a potential neuronal mediator of axon-myelin binding, was not concentrated in the paranodal regions but was diffusely distributed along the internodal regions. Collectively, these findings suggest that the myelin galactolipids are essential for the proper formation of axo-glial interactions and demonstrate that a disruption in these interactions results in profound abnormalities in the molecular organization of the paranodal axolemma.

Show MeSH
Related in: MedlinePlus