title: HGF signaling regulates Claudin-3 dynamics through its C-terminal tyrosine residues.
abstract: The hormone HGF regulates morphogenesis and regeneration of multiple organs and increased HGF signaling is strongly associated with metastatic cancer. At the cellular level, one of the distinct effects of HGF is the de-stabilization of cell-cell junctions. Several molecular mechanisms have been shown to be involved that mostly culminate at the E-cadherin adhesion complex. One of the key determinants in HGF-driven morphological changes is the actomyosin cytoskeleton whose organization and physical parameters changes upon stimulation. Here we have investigated how HGF affects the different actomyosin-associated cell-cell junction complexes, Nectin Junctions, Adherens Junctions and Tight Junctions in MDCK cells. We find that components of all complexes stay present at cell-cell contacts until their physical dissociation. We find that at cell-cell junctions, the mobility of Claudin-3, but not that of other cell-cell adhesion receptors, is affected by HGF. This depends on tyrosine residues that likely affect PDZ-domain interactions at the C-terminal tail of Claudin-3, although their phosphorylation is not directly regulated by HGF. Thus we uncovered Claudins as novel targets of HGF signaling at cell-cell junctions.
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht; Utrecht, The Netherlands.
authors.forename: Floor
authors.initials: F
authors.lastname: Twiss
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht; Utrecht, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Oldenkamp
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht; Utrecht, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Hiemstra
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics; Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences; Utrecht University; Utrecht, The Netherlands ; The Netherlands Proteomics Centre; The Netherlands.
authors.forename: Houjiang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics; Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences; Utrecht University; Utrecht, The Netherlands ; The Netherlands Proteomics Centre; The Netherlands.
authors.forename: Lucrèce
authors.initials: L
authors.lastname: Matheron
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics; Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences; Utrecht University; Utrecht, The Netherlands ; The Netherlands Proteomics Centre; The Netherlands.
authors.forename: Shabaz
authors.initials: S
authors.lastname: Mohammed
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht; Utrecht, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: de Rooij
keywords: Claudin; HGF signaling; Tight Junction; cell-cell junctions; phosphorylation; turnover