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Tight junctions in Schwann cells of peripheral myelinated axons

Tatsuo Miyamoto¹, Kazumasa Morita³, Daisuke Takemoto⁴, Kosei Takeuchi^4,5, Yuka Kitano¹, Tsuyoshi Miyakawa², Kiyomi Nakayama⁶, Yasushi Okamura⁶, Hiroyuki Sasaki^5,7, Yoshiki Miyachi³, Mikio Furuse¹, and Shoichiro Tsukita¹

¹ Department of Cell Biology, Horizontal Medical Research Organization
² Genetic Engineering and Functional Genomics Group, Horizontal Medical Research Organization
³ Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
⁴ Department of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan
⁵ KAN Research Institute Inc., Kyoto Research Park, Chudoji, Shimogyo-ku, Kyoto 600-8317, Japan
⁶ Section of Developmental Neurophysiology, Ozaki Institute for Integrative Bioscience, National Institute of Natural Sciences, Okazaki 444-8787, Japan
⁷ Department of Molecular Cell Biology, Institute of DNA Medicine, The Jikei University School of Medicine, Nishi-Shinbashi, Minato-ku, Tokyo 105, Japan

Correspondence to Shoichiro Tsukita: htsukita{at}mfour.med.kyoto-u.ac.jp

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.

Abbreviations used in this paper: CAP, compound action potential; Caspr, contactin-associated protein; CMT, Charcot-Marie-Tooth; CNS, central nervous system; ES, embryonic stem; OSP, oligodendrocyte-specific protein; PNS; peripheral nervous system; TJ, tight junction.

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