Hyper-adhesion in desmosomes: Its regulation in wound healing and possible relationship to cadherin crystal structure

David R. Garrod, Mohamed Y. Berika, William F. Bardsley, David Holmes, Lydia Tabernero

    Research output: Contribution to journalArticlepeer-review

    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 α 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.
    Original languageEnglish
    Pages (from-to)5743-5754
    Number of pages11
    JournalJournal of Cell Science
    Volume118
    Issue number24
    DOIs
    Publication statusPublished - 15 Dec 2005

    Keywords

    • Cadherin
    • Cell-cell adhesion
    • Desmosome
    • Protein kinase C
    • Wound healing

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