title: CD44 regulates tight-junction assembly and barrier function.
abstract: Upon barrier disturbance, adult CD44 knockout (KO) mice show delayed recovery of epidermal barrier function. This correlates with the loss of apical polarization of lamellar body (LB) secretion. As tight junctions (TJs) are crucial for barrier function and regulate polarized targeting of vesicles, we hypothesized that CD44 regulates TJs and associated cell polarity complexes, which in turn contributes to altered skin barrier function in CD44 KO mice. We show a delay in embryonic barrier formation associated with a loss of apical LB localization in CD44 KO mice, which correlates with alterations in TJ proteins and Par3. Simultaneously, the activity of Rac1, a major regulator of TJ barrier function, was reduced. Importantly, normalization of barrier function at E18.5 coincided with the recovery of these proteins. Tape-stripping experiments revealed that the loss of CD44 also affected TJ proteins upon induced disturbance of the barrier in adult mice. In CD44 KO keratinocytes, cell polarization and TJ barrier function were impaired. An alteration of differentiation markers was also observed, but was less pronounced than alterations of TJ proteins. Taken together, the results reveal an important function for CD44 in the assembly and function of TJs, suggesting their involvement in the skin barrier phenotype of CD44 KO mice.
authors.affiliation: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Kirschner
authors.forename: Marek
authors.initials: M
authors.lastname: Haftek
authors.forename: Carien M
authors.initials: CM
authors.lastname: Niessen
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Behne
authors.forename: Mikio
authors.initials: M
authors.lastname: Furuse
authors.forename: Ingrid
authors.initials: I
authors.lastname: Moll
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Brandner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D010641:Phenotype; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; C476399:Cd44 protein, mouse; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D018960:Hyaluronan Receptors; D009479:Neuropeptides; C115084:Pard3 protein, mouse; C484602:Rac1 protein, mouse; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C513260:Tiam1 protein, mouse; D006820:Hyaluronic Acid; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein