BPAG1-e restricts keratinocyte migration through control of adhesion stability

Magdalene Michael, Rumena Begum, Kenneth Fong, Celine Pourreyrone, Andrew P. South, John A. McGrath, Maddy Parsons

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    29 Citations (Scopus)


    Bullous pemphigoid antigen 1 (BPAG1-e, also known as BP230) is a member of the plakin family of hemidesmosome cytoskeletal linker proteins that is encoded by an isoform of the dystonin (DST) gene. Recently, we reported two unrelated families with homozygous nonsense mutations in this DST isoform that led to ultrastructural loss of hemidesmosomal inner plaques and clinical features of trauma-induced skin fragility. We now demonstrate that keratinocytes isolated from these individuals have significant defects in adhesion, as well as increased cell spreading and migration. These mutant keratinocytes also display reduced levels of ß4 integrins at the cell surface but increased total protein levels of keratin-14 and ß1 integrins. These alterations in cell behavior and protein expression were not seen in control keratinocytes in which BPAG1-e expression had been silenced by stable expression of short hairpin RNA to target DST. The failure of knockdown approaches to recapitulate the changes in morphology, adhesion, and migration seen in patient cells therefore suggests such approaches are not appropriate to study loss of this protein in vivo. The contrasting findings in keratinocytes harboring naturally occurring mutations, however, demonstrate a previously unappreciated key role for BPAG1-e in regulating keratinocyte adhesion and migration and suggest a requirement for this protein in controlling functional switching between integrin types in epithelial cells.
    Original languageEnglish
    Pages (from-to)773-782
    Number of pages10
    JournalJournal of Investigative Dermatology
    Issue number3
    Publication statusPublished - Mar 2014


    • Antigens, CD29
    • Breast
    • Carrier Proteins
    • Cell Adhesion
    • Cell Line
    • Cell Movement
    • Cytoskeletal Proteins
    • Desmosomes
    • Female
    • Humans
    • Integrin beta4
    • Keratin-14
    • Keratinocytes
    • Middle Aged
    • Mutation
    • Nerve Tissue Proteins


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