title: Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct localization and function.
abstract: The tight junction protein claudin-10 is known to exist in two isoforms, resulting from two alternative exons, 1a and 1b (Cldn10a, Cldn10b). Here, we identified and characterized another four claudin-10 splice variants in mouse and human. One (Cldn10a_v1) results from an alternative splice donor site, causing a deletion of the last 57 nucleotides of exon 1a. For each of these three variants one further splice variant was identified (Cldn10a_v2, Cldn10a_v3, Cldn10b_v1), lacking exon 4. When transfected into MDCK cells, Cldn10a, Cldn10a_v1 and Cldn10b were inserted into the tight junction, whereas isoforms of splice variants lacking exon 4 were retained in the endoplasmic reticulum. Cldn10a transfection into MDCK cells confirmed the previously described increase in paracellular anion permeability. Cldn10a_v1 transfection had no direct effect, but modulated Cldn10a-induced organic anion permeability. At variance with previous reports in MDCK-II cells, transfection of high-resistance MDCK-C7 cells with Cldn10b dramatically decreased transepithelial resistance, increased cation permeability, and changed monovalent cation selectivity from Eisenman sequence IV to X, indicating the presence of a high field-strength binding site that almost completely removes the hydration shell of the permeating cations. The extent of all these effects strongly depended on the endogenous claudins of the transfected cells.
authors.affiliation: Institute of Clinical Physiology, Charité, 12200 Berlin, Germany. dorothee.guenzel@charite.de
authors.forename: Dorothee
authors.initials: D
authors.lastname: Günzel
authors.forename: Marchel
authors.initials: M
authors.lastname: Stuiver
authors.forename: P Jaya
authors.initials: PJ
authors.lastname: Kausalya
authors.forename: Lea
authors.initials: L
authors.lastname: Haisch
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Krug
authors.forename: Rita
authors.initials: R
authors.lastname: Rosenthal
authors.forename: Iwan C
authors.initials: IC
authors.lastname: Meij
authors.forename: Walter
authors.initials: W
authors.lastname: Hunziker
authors.forename: Michael
authors.initials: M
authors.lastname: Fromm
authors.forename: Dominik
authors.initials: D
authors.lastname: Müller
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D057167:Claudins; D004285:Dogs; D017097:Electric Impedance; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005091:Exons; D006801:Humans; D017136:Ion Transport; D007668:Kidney / Q000378:metabolism*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010539:Permeability; D010750:Phosphoproteins / Q000378:metabolism; D011487:Protein Conformation; D020033:Protein Isoforms; D021381:Protein Transport; D022821:RNA Splice Sites; D019108:Tight Junctions / Q000378:metabolism*; D014162:Transfection; D062826:Zonula Occludens-1 Protein
chemical_list: D057167:Claudins; D008565:Membrane Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D022821:RNA Splice Sites; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C502009:claudin 10