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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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Electrophysiological analysis of claudin-19–deficient mice. Sciatic nerves were isolated from 10-wk-old mice (n = 10 each for Cld19+/+ and Cld19−/− mice), and field potential recordings were made to measure the CAPs. The distance between extracellular stimulation and recording electrodes was 2.5 cm. When nerves were stimulated with sufficiently large currents to elicit maximal CAP amplitude, CAPs obtained from all Cld19+/+ mice demonstrated a single-peak, smooth waveform (open arrowheads; +/+). However, in 3 out of 10 Cld19−/− mice, CAPs showed a characteristic double-peak waveform: a peak around a normal conduction velocity (open arrowheads) and an additional delayed peak (closed arrowheads; −/−). Under the stimulus intensity to elicit half-maximal CAP amplitude, this double-peak CAP waveform was reproducibly detected in Cld19−/− mice, but never in Cld19+/+ mice (not depicted). Arrows, stimulation.
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fig5: Electrophysiological analysis of claudin-19–deficient mice. Sciatic nerves were isolated from 10-wk-old mice (n = 10 each for Cld19+/+ and Cld19−/− mice), and field potential recordings were made to measure the CAPs. The distance between extracellular stimulation and recording electrodes was 2.5 cm. When nerves were stimulated with sufficiently large currents to elicit maximal CAP amplitude, CAPs obtained from all Cld19+/+ mice demonstrated a single-peak, smooth waveform (open arrowheads; +/+). However, in 3 out of 10 Cld19−/− mice, CAPs showed a characteristic double-peak waveform: a peak around a normal conduction velocity (open arrowheads) and an additional delayed peak (closed arrowheads; −/−). Under the stimulus intensity to elicit half-maximal CAP amplitude, this double-peak CAP waveform was reproducibly detected in Cld19−/− mice, but never in Cld19+/+ mice (not depicted). Arrows, stimulation.

Mentions: To directly evaluate the electrophysiological properties of the peripheral nerves in Cld19−/− mice, we made field potential recordings of isolated sciatic nerves to measure the compound action potentials (CAPs), though this recording was not technically easy mainly because of the short length of isolated mouse sciatic nerves. When nerves were stimulated with sufficiently large currents to elicit the maximal CAP amplitude, CAPs obtained from Cld19+/+ mice demonstrated a single-peak, smooth waveform. In 7 out of 10 Cld19−/− mice, CAP waveforms or population conduction velocities did not appear to be significantly different from those in Cld19+/+ mice, but in three Cld19−/− mice we noticed a significant difference in CAP waveforms. These CAPs showed a characteristic double-peak waveform: a peak around a normal conduction velocity and an additional delayed peak (Fig. 5). Interestingly, under the stimulus intensity to elicit half-maximal CAP amplitude, this double-peak CAP waveform was reproducibly detected in Cld19−/− mice (n = 10) but never in Cld19+/+ mice (n = 10; unpublished data). Although the mechanism responsible for this difference remains unclear, it is safe to say that the claudin-19 deficiency changed the conduction parameters of at least a subpopulation of myelinated fibers to reduce their conduction velocity.


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)

Electrophysiological analysis of claudin-19–deficient mice. Sciatic nerves were isolated from 10-wk-old mice (n = 10 each for Cld19+/+ and Cld19−/− mice), and field potential recordings were made to measure the CAPs. The distance between extracellular stimulation and recording electrodes was 2.5 cm. When nerves were stimulated with sufficiently large currents to elicit maximal CAP amplitude, CAPs obtained from all Cld19+/+ mice demonstrated a single-peak, smooth waveform (open arrowheads; +/+). However, in 3 out of 10 Cld19−/− mice, CAPs showed a characteristic double-peak waveform: a peak around a normal conduction velocity (open arrowheads) and an additional delayed peak (closed arrowheads; −/−). Under the stimulus intensity to elicit half-maximal CAP amplitude, this double-peak CAP waveform was reproducibly detected in Cld19−/− mice, but never in Cld19+/+ mice (not depicted). Arrows, stimulation.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Electrophysiological analysis of claudin-19–deficient mice. Sciatic nerves were isolated from 10-wk-old mice (n = 10 each for Cld19+/+ and Cld19−/− mice), and field potential recordings were made to measure the CAPs. The distance between extracellular stimulation and recording electrodes was 2.5 cm. When nerves were stimulated with sufficiently large currents to elicit maximal CAP amplitude, CAPs obtained from all Cld19+/+ mice demonstrated a single-peak, smooth waveform (open arrowheads; +/+). However, in 3 out of 10 Cld19−/− mice, CAPs showed a characteristic double-peak waveform: a peak around a normal conduction velocity (open arrowheads) and an additional delayed peak (closed arrowheads; −/−). Under the stimulus intensity to elicit half-maximal CAP amplitude, this double-peak CAP waveform was reproducibly detected in Cld19−/− mice, but never in Cld19+/+ mice (not depicted). Arrows, stimulation.
Mentions: To directly evaluate the electrophysiological properties of the peripheral nerves in Cld19−/− mice, we made field potential recordings of isolated sciatic nerves to measure the compound action potentials (CAPs), though this recording was not technically easy mainly because of the short length of isolated mouse sciatic nerves. When nerves were stimulated with sufficiently large currents to elicit the maximal CAP amplitude, CAPs obtained from Cld19+/+ mice demonstrated a single-peak, smooth waveform. In 7 out of 10 Cld19−/− mice, CAP waveforms or population conduction velocities did not appear to be significantly different from those in Cld19+/+ mice, but in three Cld19−/− mice we noticed a significant difference in CAP waveforms. These CAPs showed a characteristic double-peak waveform: a peak around a normal conduction velocity and an additional delayed peak (Fig. 5). Interestingly, under the stimulus intensity to elicit half-maximal CAP amplitude, this double-peak CAP waveform was reproducibly detected in Cld19−/− mice (n = 10) but never in Cld19+/+ mice (n = 10; unpublished data). Although the mechanism responsible for this difference remains unclear, it is safe to say that the claudin-19 deficiency changed the conduction parameters of at least a subpopulation of myelinated fibers to reduce their conduction velocity.

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