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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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Abundant expression of claudin-19 in PNS. (A) Northern blots of mouse claudin-19 expression. Aliquots of total RNA (1 μg) isolated from the mouse sciatic nerve and the whole brain were separated and transferred onto a nylon membrane. This membrane (left) and mouse multiple tissue membranes (right; SeeGene) were probed with a digoxigenin-labeled claudin-19 RNA probe. Claudin-19 mRNAs were detected as major 1.0-kb and minor 4.7- and 1.8-kb bands (arrowheads) in large amounts in the sciatic nerve and the kidney. In the kidney, claudin-19 appeared to be expressed and concentrated at TJs in renal tubules, but, in this study, we did not discuss this point. (B) TJ strand–like structures reconstituted in L fibroblasts exogenously expressing mouse claudin-19. Freeze-fracture replica electron microscopy identified these strands in the cell–cell contact regions. Bar, 500 nm. (C) Specificity of anti–claudin-19 pAb. GST fusion proteins with the cytoplasmic domains of claudin-1 to -16 as well as the cytoplasmic domain of claudin-19 were produced in E. coli. The lysates of E. coli were separated by SDS-PAGE (CBB), followed by immunoblotting with anti–claudin-19 pAb, which was raised in this study. Bars indicate molecular masses of 31 and 21 kD from the top. (D) PNS-specific expression of claudin-19. Transverse frozen sections of the mouse spinal cord with the ventral root were double stained with antineurofilament mAb (red)/anti–claudin-19 pAb (green) or antineurofilament mAb (red)/anti–claudin-11 pAb (green). In the nervous system, the expression of claudin-19 was restricted to the PNS (PN). In contrast, as previously reported (Morita et al., 1999b), claudin-11 was expressed in the CNS (CN) but not in the PNS (PN). Bar, 50 μm.
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fig1: Abundant expression of claudin-19 in PNS. (A) Northern blots of mouse claudin-19 expression. Aliquots of total RNA (1 μg) isolated from the mouse sciatic nerve and the whole brain were separated and transferred onto a nylon membrane. This membrane (left) and mouse multiple tissue membranes (right; SeeGene) were probed with a digoxigenin-labeled claudin-19 RNA probe. Claudin-19 mRNAs were detected as major 1.0-kb and minor 4.7- and 1.8-kb bands (arrowheads) in large amounts in the sciatic nerve and the kidney. In the kidney, claudin-19 appeared to be expressed and concentrated at TJs in renal tubules, but, in this study, we did not discuss this point. (B) TJ strand–like structures reconstituted in L fibroblasts exogenously expressing mouse claudin-19. Freeze-fracture replica electron microscopy identified these strands in the cell–cell contact regions. Bar, 500 nm. (C) Specificity of anti–claudin-19 pAb. GST fusion proteins with the cytoplasmic domains of claudin-1 to -16 as well as the cytoplasmic domain of claudin-19 were produced in E. coli. The lysates of E. coli were separated by SDS-PAGE (CBB), followed by immunoblotting with anti–claudin-19 pAb, which was raised in this study. Bars indicate molecular masses of 31 and 21 kD from the top. (D) PNS-specific expression of claudin-19. Transverse frozen sections of the mouse spinal cord with the ventral root were double stained with antineurofilament mAb (red)/anti–claudin-19 pAb (green) or antineurofilament mAb (red)/anti–claudin-11 pAb (green). In the nervous system, the expression of claudin-19 was restricted to the PNS (PN). In contrast, as previously reported (Morita et al., 1999b), claudin-11 was expressed in the CNS (CN) but not in the PNS (PN). Bar, 50 μm.

Mentions: Northern blotting revealed that claudin-19 was expressed in large amounts in the PNS. Other tissues, including the brain, did not give strong signals, but the kidney expressed this claudin in fairly large amounts (Fig. 1 A). Similar to other claudin species, claudin-19 showed an ability to polymerize to reconstituted TJ strand–like structures in cell–cell contact regions when overexpressed in mouse L fibroblasts (Fig. 1 B). These findings suggested that claudin-19 constituted TJ strands in some types of cells within peripheral nerves. In peripheral nerves, three types of cells have been reported to bear TJs or TJ-like structures: endothelial cells of blood vessels, mesothelial cells in the perineurium, and Schwann cells of myelinated axons.


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)

Abundant expression of claudin-19 in PNS. (A) Northern blots of mouse claudin-19 expression. Aliquots of total RNA (1 μg) isolated from the mouse sciatic nerve and the whole brain were separated and transferred onto a nylon membrane. This membrane (left) and mouse multiple tissue membranes (right; SeeGene) were probed with a digoxigenin-labeled claudin-19 RNA probe. Claudin-19 mRNAs were detected as major 1.0-kb and minor 4.7- and 1.8-kb bands (arrowheads) in large amounts in the sciatic nerve and the kidney. In the kidney, claudin-19 appeared to be expressed and concentrated at TJs in renal tubules, but, in this study, we did not discuss this point. (B) TJ strand–like structures reconstituted in L fibroblasts exogenously expressing mouse claudin-19. Freeze-fracture replica electron microscopy identified these strands in the cell–cell contact regions. Bar, 500 nm. (C) Specificity of anti–claudin-19 pAb. GST fusion proteins with the cytoplasmic domains of claudin-1 to -16 as well as the cytoplasmic domain of claudin-19 were produced in E. coli. The lysates of E. coli were separated by SDS-PAGE (CBB), followed by immunoblotting with anti–claudin-19 pAb, which was raised in this study. Bars indicate molecular masses of 31 and 21 kD from the top. (D) PNS-specific expression of claudin-19. Transverse frozen sections of the mouse spinal cord with the ventral root were double stained with antineurofilament mAb (red)/anti–claudin-19 pAb (green) or antineurofilament mAb (red)/anti–claudin-11 pAb (green). In the nervous system, the expression of claudin-19 was restricted to the PNS (PN). In contrast, as previously reported (Morita et al., 1999b), claudin-11 was expressed in the CNS (CN) but not in the PNS (PN). Bar, 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2171943&req=5

fig1: Abundant expression of claudin-19 in PNS. (A) Northern blots of mouse claudin-19 expression. Aliquots of total RNA (1 μg) isolated from the mouse sciatic nerve and the whole brain were separated and transferred onto a nylon membrane. This membrane (left) and mouse multiple tissue membranes (right; SeeGene) were probed with a digoxigenin-labeled claudin-19 RNA probe. Claudin-19 mRNAs were detected as major 1.0-kb and minor 4.7- and 1.8-kb bands (arrowheads) in large amounts in the sciatic nerve and the kidney. In the kidney, claudin-19 appeared to be expressed and concentrated at TJs in renal tubules, but, in this study, we did not discuss this point. (B) TJ strand–like structures reconstituted in L fibroblasts exogenously expressing mouse claudin-19. Freeze-fracture replica electron microscopy identified these strands in the cell–cell contact regions. Bar, 500 nm. (C) Specificity of anti–claudin-19 pAb. GST fusion proteins with the cytoplasmic domains of claudin-1 to -16 as well as the cytoplasmic domain of claudin-19 were produced in E. coli. The lysates of E. coli were separated by SDS-PAGE (CBB), followed by immunoblotting with anti–claudin-19 pAb, which was raised in this study. Bars indicate molecular masses of 31 and 21 kD from the top. (D) PNS-specific expression of claudin-19. Transverse frozen sections of the mouse spinal cord with the ventral root were double stained with antineurofilament mAb (red)/anti–claudin-19 pAb (green) or antineurofilament mAb (red)/anti–claudin-11 pAb (green). In the nervous system, the expression of claudin-19 was restricted to the PNS (PN). In contrast, as previously reported (Morita et al., 1999b), claudin-11 was expressed in the CNS (CN) but not in the PNS (PN). Bar, 50 μm.
Mentions: Northern blotting revealed that claudin-19 was expressed in large amounts in the PNS. Other tissues, including the brain, did not give strong signals, but the kidney expressed this claudin in fairly large amounts (Fig. 1 A). Similar to other claudin species, claudin-19 showed an ability to polymerize to reconstituted TJ strand–like structures in cell–cell contact regions when overexpressed in mouse L fibroblasts (Fig. 1 B). These findings suggested that claudin-19 constituted TJ strands in some types of cells within peripheral nerves. In peripheral nerves, three types of cells have been reported to bear TJs or TJ-like structures: endothelial cells of blood vessels, mesothelial cells in the perineurium, and Schwann cells of myelinated axons.

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