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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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Subcellular distribution of claudin-19 in peripheral myelinated axons. (A) Schematic view of a myelinated axon in the PNS. In the left panel, one myelinating Schwann cell has been unrolled, revealing the regions that form compact myelin (asterisks), the outer mesaxon (OMA), the inner mesaxon (IMA), the Schmidt-Lanterman incisures (SL), and the paranode (PN). On both sides of individual, unrolled flat Schwann cells, TJ strand–like structures have been reported to form a circumferential belt and also to occur along incisures. Continuous and dotted green lines represent these strands on this and the far side of unrolled cells, respectively. When these cells are rolled around axons (right), the continuous line makes paired strands with the dotted line on the other side to form TJ-like structures, the localization of which in the internodal segment is very complex. TJ-like structures are densely and spirally concentrated at the Schmidt-Lanterman incisures (SL) and the paranode, and occur as two parallel lines along outer (1) and inner (2) mesaxons. (B) Whole-mount double staining of teased sciatic nerve fibers of 10-wk-old, wild-type mice with anti–claudin-19 pAb (green) and antineurofilament mAb (red). The distribution of claudin-19 coincided well with the expected localization of TJ-like structures presented in the right panel of A. Single arrowheads, paranodal regions; double arrowheads, Schmidt-Lanterman incisures; arrows, outer/inner mesaxons. In the bottom panel, one nodal/paranodal region was double stained with rat Caspr/Paranodin-pAb (red) and rabbit anti–claudin-19 pAb (green). Note that at the paranode, claudin-19 was more outwardly distributed than Caspr/Paranodin. Bars: (top) 5 μm; (bottom) 3 μm.
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fig2: Subcellular distribution of claudin-19 in peripheral myelinated axons. (A) Schematic view of a myelinated axon in the PNS. In the left panel, one myelinating Schwann cell has been unrolled, revealing the regions that form compact myelin (asterisks), the outer mesaxon (OMA), the inner mesaxon (IMA), the Schmidt-Lanterman incisures (SL), and the paranode (PN). On both sides of individual, unrolled flat Schwann cells, TJ strand–like structures have been reported to form a circumferential belt and also to occur along incisures. Continuous and dotted green lines represent these strands on this and the far side of unrolled cells, respectively. When these cells are rolled around axons (right), the continuous line makes paired strands with the dotted line on the other side to form TJ-like structures, the localization of which in the internodal segment is very complex. TJ-like structures are densely and spirally concentrated at the Schmidt-Lanterman incisures (SL) and the paranode, and occur as two parallel lines along outer (1) and inner (2) mesaxons. (B) Whole-mount double staining of teased sciatic nerve fibers of 10-wk-old, wild-type mice with anti–claudin-19 pAb (green) and antineurofilament mAb (red). The distribution of claudin-19 coincided well with the expected localization of TJ-like structures presented in the right panel of A. Single arrowheads, paranodal regions; double arrowheads, Schmidt-Lanterman incisures; arrows, outer/inner mesaxons. In the bottom panel, one nodal/paranodal region was double stained with rat Caspr/Paranodin-pAb (red) and rabbit anti–claudin-19 pAb (green). Note that at the paranode, claudin-19 was more outwardly distributed than Caspr/Paranodin. Bars: (top) 5 μm; (bottom) 3 μm.

Mentions: For this insulation, two distinct types of paracellular pathways must be electrically sealed: the axo-glial junctions at the paranode flanking the node of Ranvier and the intermembranous spaces within individual glial cells. Interestingly, the axo-glial paranodal junctions resemble septate junctions that are thought to be responsible for electrical sealing in invertebrates in general (Rosenbluth, 1976; Einheber et al., 1997); thus, this paranodal junction has attracted much interest in the past few years and the molecular architecture of this junction is being rapidly unraveled (Peles and Salzer, 2000; Pedraza et al., 2001; Spiegel and Peles, 2002; Poliak and Peles, 2003). On the other hand, the intermembranous spaces within individual glial cells have been considered to be mostly sealed by compact myelin, but, in addition, old electron microscopic observations indicated the existence of tight junction (TJ)–like structures that might also be involved in the intermembranous sealing of glial cells (Dermietzel, 1974; Mugnaini and Schnapp, 1974; Reale et al., 1975; Schnapp and Mugnaini, 1976; Sandri et al., 1977; Tabira et al., 1978; Dermietzel and Kroczek, 1980; Shinowara et al., 1980; see Fig. 2). However, a knowledge of the molecular components of these TJ-like structures in glial cells has been lacking for some time.


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)

Subcellular distribution of claudin-19 in peripheral myelinated axons. (A) Schematic view of a myelinated axon in the PNS. In the left panel, one myelinating Schwann cell has been unrolled, revealing the regions that form compact myelin (asterisks), the outer mesaxon (OMA), the inner mesaxon (IMA), the Schmidt-Lanterman incisures (SL), and the paranode (PN). On both sides of individual, unrolled flat Schwann cells, TJ strand–like structures have been reported to form a circumferential belt and also to occur along incisures. Continuous and dotted green lines represent these strands on this and the far side of unrolled cells, respectively. When these cells are rolled around axons (right), the continuous line makes paired strands with the dotted line on the other side to form TJ-like structures, the localization of which in the internodal segment is very complex. TJ-like structures are densely and spirally concentrated at the Schmidt-Lanterman incisures (SL) and the paranode, and occur as two parallel lines along outer (1) and inner (2) mesaxons. (B) Whole-mount double staining of teased sciatic nerve fibers of 10-wk-old, wild-type mice with anti–claudin-19 pAb (green) and antineurofilament mAb (red). The distribution of claudin-19 coincided well with the expected localization of TJ-like structures presented in the right panel of A. Single arrowheads, paranodal regions; double arrowheads, Schmidt-Lanterman incisures; arrows, outer/inner mesaxons. In the bottom panel, one nodal/paranodal region was double stained with rat Caspr/Paranodin-pAb (red) and rabbit anti–claudin-19 pAb (green). Note that at the paranode, claudin-19 was more outwardly distributed than Caspr/Paranodin. Bars: (top) 5 μm; (bottom) 3 μm.
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Related In: Results  -  Collection

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fig2: Subcellular distribution of claudin-19 in peripheral myelinated axons. (A) Schematic view of a myelinated axon in the PNS. In the left panel, one myelinating Schwann cell has been unrolled, revealing the regions that form compact myelin (asterisks), the outer mesaxon (OMA), the inner mesaxon (IMA), the Schmidt-Lanterman incisures (SL), and the paranode (PN). On both sides of individual, unrolled flat Schwann cells, TJ strand–like structures have been reported to form a circumferential belt and also to occur along incisures. Continuous and dotted green lines represent these strands on this and the far side of unrolled cells, respectively. When these cells are rolled around axons (right), the continuous line makes paired strands with the dotted line on the other side to form TJ-like structures, the localization of which in the internodal segment is very complex. TJ-like structures are densely and spirally concentrated at the Schmidt-Lanterman incisures (SL) and the paranode, and occur as two parallel lines along outer (1) and inner (2) mesaxons. (B) Whole-mount double staining of teased sciatic nerve fibers of 10-wk-old, wild-type mice with anti–claudin-19 pAb (green) and antineurofilament mAb (red). The distribution of claudin-19 coincided well with the expected localization of TJ-like structures presented in the right panel of A. Single arrowheads, paranodal regions; double arrowheads, Schmidt-Lanterman incisures; arrows, outer/inner mesaxons. In the bottom panel, one nodal/paranodal region was double stained with rat Caspr/Paranodin-pAb (red) and rabbit anti–claudin-19 pAb (green). Note that at the paranode, claudin-19 was more outwardly distributed than Caspr/Paranodin. Bars: (top) 5 μm; (bottom) 3 μm.
Mentions: For this insulation, two distinct types of paracellular pathways must be electrically sealed: the axo-glial junctions at the paranode flanking the node of Ranvier and the intermembranous spaces within individual glial cells. Interestingly, the axo-glial paranodal junctions resemble septate junctions that are thought to be responsible for electrical sealing in invertebrates in general (Rosenbluth, 1976; Einheber et al., 1997); thus, this paranodal junction has attracted much interest in the past few years and the molecular architecture of this junction is being rapidly unraveled (Peles and Salzer, 2000; Pedraza et al., 2001; Spiegel and Peles, 2002; Poliak and Peles, 2003). On the other hand, the intermembranous spaces within individual glial cells have been considered to be mostly sealed by compact myelin, but, in addition, old electron microscopic observations indicated the existence of tight junction (TJ)–like structures that might also be involved in the intermembranous sealing of glial cells (Dermietzel, 1974; Mugnaini and Schnapp, 1974; Reale et al., 1975; Schnapp and Mugnaini, 1976; Sandri et al., 1977; Tabira et al., 1978; Dermietzel and Kroczek, 1980; Shinowara et al., 1980; see Fig. 2). However, a knowledge of the molecular components of these TJ-like structures in glial cells has been lacking for some time.

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