title: Claudin-17 forms tight junction channels with distinct anion selectivity.
abstract: Barrier properties of tight junctions are determined by the claudin protein family. Many claudins seal this barrier, but others form paracellular channels. Among these, no claudins with general and clear-cut anion selectivity have yet been described, while for claudin-10a and claudin-4, only circumstantial or small anion selectivities have been shown. A claudin with unknown function and tissue distribution is claudin-17. We characterized claudin-17 by overexpression and knock-down in two renal cell lines. Overexpression in MDCK C7 cell layers caused a threefold increase in paracellular anion permeability and switched these cells from cation- to anion-selective. Knockdown in LLC-PK(1) cells indorsed the finding of claudin-17-based anion channels. Mutagenesis revealed that claudin-17 anion selectivity critically depends on a positive charge at position 65. Claudin-17 expression was found in two organs: marginal in brain but abundant in kidney, where expression was intense in proximal tubules and gradually decreased towards distal segments. As claudin-17 is predominantly expressed in proximal nephrons, which exhibit substantial, though molecularly not defined, paracellular chloride reabsorption, we suggest that claudin-17 has a unique physiological function in this process. In conclusion, claudin-17 forms channels within tight junctions with distinct anion preference.
authors.affiliation: Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Krug
authors.forename: Dorothee
authors.initials: D
authors.lastname: Günzel
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Conrad
authors.forename: Rita
authors.initials: R
authors.lastname: Rosenthal
authors.forename: Anja
authors.initials: A
authors.lastname: Fromm
authors.forename: Salah
authors.initials: S
authors.lastname: Amasheh
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Schulzke
authors.forename: Michael
authors.initials: M
authors.lastname: Fromm
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D015153:Blotting, Western; D002412:Cations / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism*; D057167:Claudins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D018374:LLC-PK1 Cells; D051379:Mice; D008969:Molecular Sequence Data; D009399:Nephrons / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013552:Swine; D019108:Tight Junctions / Q000502:physiology*
chemical_list: D020346:Aquaporins; D001639:Bicarbonates; D002412:Cations; D002712:Chlorides; D057167:Claudins; D012333:RNA, Messenger