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Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice.

Miyamoto T, Morita K, Takemoto D, Takeuchi K, Kitano Y, Miyakawa T, Nakayama K, Okamura Y, Sasaki H, Miyachi Y, Furuse M, Tsukita S - J. Cell Biol. (2005)

Bottom Line: Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits.Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons.These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Graduate School of Medicine, Kyoto University, Japan.

ABSTRACT
Tight junction (TJ)-like structures have been reported in Schwann cells, but their molecular composition and physiological function remain elusive. We found that claudin-19, a novel member of the claudin family (TJ adhesion molecules in epithelia), constituted these structures. Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits. Electrophysiological analyses showed that the claudin-19 deficiency affected the nerve conduction of peripheral myelinated fibers. Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons. These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.

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Overall morphology of the node of Ranvier of peripheral myelinated axons of claudin-19–deficient mice. Longitudinal sectional views of the node of Ranvier were compared by ultrathin section electron microscopy between Cld19+/+ and Cld19−/− saphenous nerves. The claudin-19 deficiency did not appear to affect the overall morphology of the node of Ranvier, including the paranodal region (left). At a higher magnification in the paranodal region of both Cld19+/+ and Cld19−/− axons, electron-dense transverse bands between terminal loops and axonal membranes were clearly observed (arrowheads). Asterisks, paranodal terminal loops; Ax, axon. Bars: (left) 1 μm; (right) 100 nm.
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fig7: Overall morphology of the node of Ranvier of peripheral myelinated axons of claudin-19–deficient mice. Longitudinal sectional views of the node of Ranvier were compared by ultrathin section electron microscopy between Cld19+/+ and Cld19−/− saphenous nerves. The claudin-19 deficiency did not appear to affect the overall morphology of the node of Ranvier, including the paranodal region (left). At a higher magnification in the paranodal region of both Cld19+/+ and Cld19−/− axons, electron-dense transverse bands between terminal loops and axonal membranes were clearly observed (arrowheads). Asterisks, paranodal terminal loops; Ax, axon. Bars: (left) 1 μm; (right) 100 nm.

Mentions: The claudin-19 deficiency did not appear to affect the overall organization of the node of Ranvier (Fig. 7). In longitudinal sections of myelinated nerves in both Cld19+/+ and Cld19−/− axons, the nodal region was clearly discernible between the terminal loops of Schwann cells. Although whole-mount immunostaining revealed that in Cld19−/− myelinated axons, claudin-19 was completely undetectable in paranodal regions (unpublished data), the terminal loops appeared to be normal. Unfortunately, however, it was technically difficult to conclusively demonstrate the existence and/or absence of TJ-like structures between these loops of Cld19+/+ and Cld19−/− axons by ultrathin section and by freeze-fracture replica electron microscopy. Importantly, also in the paranodal region of Cld19−/− axons, electron-dense transverse bands between terminal loops and axonal membranes were observed with a normal appearance.


Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice.

Miyamoto T, Morita K, Takemoto D, Takeuchi K, Kitano Y, Miyakawa T, Nakayama K, Okamura Y, Sasaki H, Miyachi Y, Furuse M, Tsukita S - J. Cell Biol. (2005)

Overall morphology of the node of Ranvier of peripheral myelinated axons of claudin-19–deficient mice. Longitudinal sectional views of the node of Ranvier were compared by ultrathin section electron microscopy between Cld19+/+ and Cld19−/− saphenous nerves. The claudin-19 deficiency did not appear to affect the overall morphology of the node of Ranvier, including the paranodal region (left). At a higher magnification in the paranodal region of both Cld19+/+ and Cld19−/− axons, electron-dense transverse bands between terminal loops and axonal membranes were clearly observed (arrowheads). Asterisks, paranodal terminal loops; Ax, axon. Bars: (left) 1 μm; (right) 100 nm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171943&req=5

fig7: Overall morphology of the node of Ranvier of peripheral myelinated axons of claudin-19–deficient mice. Longitudinal sectional views of the node of Ranvier were compared by ultrathin section electron microscopy between Cld19+/+ and Cld19−/− saphenous nerves. The claudin-19 deficiency did not appear to affect the overall morphology of the node of Ranvier, including the paranodal region (left). At a higher magnification in the paranodal region of both Cld19+/+ and Cld19−/− axons, electron-dense transverse bands between terminal loops and axonal membranes were clearly observed (arrowheads). Asterisks, paranodal terminal loops; Ax, axon. Bars: (left) 1 μm; (right) 100 nm.
Mentions: The claudin-19 deficiency did not appear to affect the overall organization of the node of Ranvier (Fig. 7). In longitudinal sections of myelinated nerves in both Cld19+/+ and Cld19−/− axons, the nodal region was clearly discernible between the terminal loops of Schwann cells. Although whole-mount immunostaining revealed that in Cld19−/− myelinated axons, claudin-19 was completely undetectable in paranodal regions (unpublished data), the terminal loops appeared to be normal. Unfortunately, however, it was technically difficult to conclusively demonstrate the existence and/or absence of TJ-like structures between these loops of Cld19+/+ and Cld19−/− axons by ultrathin section and by freeze-fracture replica electron microscopy. Importantly, also in the paranodal region of Cld19−/− axons, electron-dense transverse bands between terminal loops and axonal membranes were observed with a normal appearance.

Bottom Line: Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits.Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons.These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Graduate School of Medicine, Kyoto University, Japan.

ABSTRACT
Tight junction (TJ)-like structures have been reported in Schwann cells, but their molecular composition and physiological function remain elusive. We found that claudin-19, a novel member of the claudin family (TJ adhesion molecules in epithelia), constituted these structures. Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits. Electrophysiological analyses showed that the claudin-19 deficiency affected the nerve conduction of peripheral myelinated fibers. Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons. These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.

Show MeSH
Related in: MedlinePlus