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

研究成果: Article同行評審

29 引文 斯高帕斯(Scopus)

摘要

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 β4 integrins at the cell surface but increased total protein levels of keratin-14 and β1 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.

原文English
頁(從 - 到)773-782
頁數10
期刊Journal of Investigative Dermatology
134
發行號3
DOIs
出版狀態Published - 2014 3月

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子生物學
  • 皮膚科
  • 細胞生物學

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