title: Desmoglein 3 regulates membrane trafficking of cadherins, an implication in cell-cell adhesion.
abstract: E-cadherin mediated cell-cell adhesion plays a critical role in epithelial cell polarization and morphogenesis. Our recent studies suggest that the desmosomal cadherin, desmoglein 3 (Dsg3) cross talks with E-cadherin and regulates its adhesive function in differentiating keratinocytes. However, the underlying mechanism remains not fully elucidated. Since E-cadherin trafficking has been recognized to be a central determinant in cell-cell adhesion and homeostasis we hypothesize that Dsg3 may play a role in regulating E-cadherin trafficking and hence the cell-cell adhesion. Here we investigated this hypothesis in cells with loss of Dsg3 function through RNAi mediated Dsg3 knockdown or the stable expression of the truncated mutant Dsg3ΔC. Our results showed that loss of Dsg3 resulted in compromised cell-cell adhesion and reduction of adherens junction and desmosome protein expression as well as the cortical F-actin formation. As a consequence, cells failed to polarize but instead displayed aberrant cell flattening. Furthermore, retardation of E-cadherin internalization and recycling was consistently observed in these cells during the process of calcium induced junction assembling. In contrast, enhanced cadherin endocytosis was detected in cells with overexpression of Dsg3 compared to control cells. Importantly, this altered cadherin trafficking was found to be coincided with the reduced expression and activity of Rab proteins, including Rab5, Rab7 and Rab11 which are known to be involved in E-cadherin trafficking. Taken together, our findings suggest that Dsg3 functions as a key in cell-cell adhesion through at least a mechanism of regulating E-cadherin membrane trafficking.
authors.affiliation: a Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London, School of Medicine and Dentistry , Queen Mary University of London , Whitechapel, London , UK.
authors.forename: Hanan
authors.initials: H
authors.lastname: Moftah
authors.affiliation: a Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London, School of Medicine and Dentistry , Queen Mary University of London , Whitechapel, London , UK.
authors.forename: Kasuni
authors.initials: K
authors.lastname: Dias
authors.affiliation: a Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London, School of Medicine and Dentistry , Queen Mary University of London , Whitechapel, London , UK.
authors.forename: Ehsanul Hoque
authors.initials: EH
authors.lastname: Apu
authors.affiliation: a Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London, School of Medicine and Dentistry , Queen Mary University of London , Whitechapel, London , UK.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: a Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London, School of Medicine and Dentistry , Queen Mary University of London , Whitechapel, London , UK.
authors.forename: Jutamas
authors.initials: J
authors.lastname: Uttagomol
authors.affiliation: a Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London, School of Medicine and Dentistry , Queen Mary University of London , Whitechapel, London , UK.
authors.forename: Lesley
authors.initials: L
authors.lastname: Bergmeier
authors.affiliation: b Barts Cancer Institute, John Vane Science Center , Charterhouse Square, London , UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kermorgant
authors.affiliation: a Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London, School of Medicine and Dentistry , Queen Mary University of London , Whitechapel, London , UK.
authors.forename: Hong
authors.initials: H
authors.lastname: Wan
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics*; D002460:Cell Line; D051184:Desmoglein 3 / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D021381:Protein Transport / Q000235:genetics
chemical_list: D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3
keywords: E-cadherin trafficking; adherens junction; desmoglein 3; desmosome; epithelial cells; intercellular junction