title: Hyper-adhesion in desmosomes: its regulation in wound healing and possible relationship to cadherin crystal structure.
abstract: The resistance of tissues to physical stress is dependent upon strong cell-cell adhesion in which desmosomes play a crucial role. We propose that desmosomes fulfil this function by adopting a more strongly adhesive state, hyper-adhesion, than other junctions. We show that the hyper-adhesive desmosomes in epidermis resist disruption by ethylene glycol bis(2-aminoethyl ether)-N,N,N'N'-tetraacetic acid (EGTA) and are thus independent of Ca2+. We propose that Ca2+ independence is the normal condition for tissue desmosomes. Ca2+ independence is associated with an organised arrangement of the intercellular adhesive material exemplified by a dense midline. When epidermis is wounded, desmosomes in the wound-edge epithelium lose hyper-adhesiveness and become Ca2+ dependent, i.e. readily dissociated by EGTA. Ca2+-dependent desmosomes lack a midline and show narrowing of the intercellular space. We suggest that this indicates a less-organised, weakly adhesive arrangement of the desmosomal cadherins, resembling classical cadherins in adherens junctions. Transition to Ca2+ dependence on wounding is accompanied by relocalisation of protein kinase C alpha to desmosomal plaques suggesting that an 'inside-out' transmembrane signal is responsible for changing desmosomal adhesiveness. We model hyper-adhesive desmosomes using the crystal packing observed for the ectodomain of C-cadherin and show how the regularity of this 3D array provides a possible explanation for Ca2+ independence.
authors.affiliation: Faculty of Life Sciences, Michael Smith Building, Oxford Road, University of Manchester, Manchester, M13 9PT, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Garrod
authors.forename: Mohamed Y
authors.initials: MY
authors.lastname: Berika
authors.forename: William F
authors.initials: WF
authors.lastname: Bardsley
authors.forename: David
authors.initials: D
authors.lastname: Holmes
authors.forename: Lydia
authors.initials: L
authors.lastname: Tabernero
mesh_terms: D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003896:Desmosomes / Q000378:metabolism* / Q000648:ultrastructure; D004533:Egtazic Acid / Q000494:pharmacology; D004817:Epidermis / Q000293:injuries / Q000378:metabolism* / Q000648:ultrastructure; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D051571:Protein Kinase C-alpha / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing / Q000502:physiology*
chemical_list: D015820:Cadherins; D004533:Egtazic Acid; D051571:Protein Kinase C-alpha; D002118:Calcium