title: Claudin-21 Has a Paracellular Channel Role at Tight Junctions.
abstract: Claudin protein family members, of which there are at least 27 in humans and mice, polymerize to form tight junctions (TJs) between epithelial cells, in a tissue- and developmental stage-specific manner. Claudins have a paracellular barrier function. In addition, certain claudins function as paracellular channels for small ions and/or solutes by forming selective pores at the TJs, although the specific claudins involved and their functional mechanisms are still in question. Here we show for the first time that claudin-21, which is more highly expressed in the embryonic than the postnatal stages, acts as a paracellular channel for small cations, such as Na(+), similar to the typical channel-type claudins claudin-2 and -15. Claudin-21 also allows the paracellular passage of larger solutes. Our findings suggest that claudin-21-based TJs allow the passage of small and larger solutes by both paracellular channel-based and some additional mechanisms.
authors.affiliation: Graduate School of Medicine/Frontier Bioscience, Osaka University, Suita, Osaka, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Graduate School of Medicine/Frontier Bioscience, Osaka University, Suita, Osaka, Japan.
authors.forename: Hiroka
authors.initials: H
authors.lastname: Kashihara
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Cellular and Structural Physiology Institute (CeSPI), Nagoya University, Nagoya, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Tani
authors.affiliation: Cellular and Structural Physiology Institute (CeSPI), Nagoya University, Nagoya, Japan Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Nagoya, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujiyoshi
authors.affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mineta
authors.affiliation: Department of Biology, School of Medicine, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Graduate School of Medicine/Frontier Bioscience, Osaka University, Suita, Osaka, Japan atamura@biosci.med.osaka-u.ac.jp atsukita@biosci.med.osaka-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tamura
authors.affiliation: Graduate School of Medicine/Frontier Bioscience, Osaka University, Suita, Osaka, Japan atamura@biosci.med.osaka-u.ac.jp atsukita@biosci.med.osaka-u.ac.jp.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002414:Cations, Monovalent / Q000378:metabolism; D002460:Cell Line; D057167:Claudins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D012964:Sodium / Q000378:metabolism; D019108:Tight Junctions / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D002414:Cations, Monovalent; C000609265:Claudin-21 protein, mouse; D057167:Claudins; D012964:Sodium