A previously unreported function of Β1 B integrin isoform in caspase-8-dependent integrin-mediated keratinocyte death

Roberta Lotti, Alessandra Marconi, Francesca Truzzi, Katiuscia Dallaglio, Claudia Gemelli, Riccardo G. Borroni, Elisabetta Palazzo, Carlo Pincelli

Research output: Contribution to journalArticle

Abstract

Integrins regulate adhesive cell-matrix interactions and mediate survival signals. On the other hand, unligated or free cytoplasmic fragments of integrins induce apoptosis in many cell types (integrin-mediated death). We have previously shown that Β1 integrin expression protects keratinocyte stem cells from anoikis, whereas the role of the Β1 B integrin isoform has not been clarified. In this study we report that suspended keratinocytes undergo apoptosis through the activation of caspase-8, independently of the Fas/Fas ligand system. Indeed, anti-Β1 integrin-neutralizing antibodies induced apoptosis in short hairpin RNA Fas-associated death domain-treated cells. Moreover, before and during suspension, caspase-8 directly associated with Β1 integrin, which in turn internalized and progressively degraded, shedding the cytoplasmic domain. Β1 B was expressed only in the cytoplasm in a perinuclear manner and remained unaltered during suspension. At 24 hours, as Β1 A was located close to the nucleus, Β1 B colocalized with Β1 A and coimmunoprecipitated with caspase-8. Caspase-8 was activated earlier in Β1 B integrin-transfected keratinocytes, and these cells underwent a higher rate of apoptosis than mock cells. In contrast, caspase-8 was not activated in small interfering RNA (siRNA) Β1 B-transfected cells. These results indicate that when Β1 A is unligated, Β1 B is responsible for integrin-mediated death in human keratinocytes.

Original languageEnglish
Pages (from-to)2569-2577
Number of pages9
JournalJournal of Investigative Dermatology
Volume130
Issue number11
DOIs
Publication statusPublished - Nov 2010

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ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

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