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

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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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Caspase 8
Keratinocytes
Integrins
Protein Isoforms
Apoptosis
Small Interfering RNA
Suspensions
Anoikis
Fas Ligand Protein
Neutralizing Antibodies
Stem cells
Cell Communication
Adhesives
Cytoplasm
Stem Cells
Chemical activation
Cells
Survival

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

A previously unreported function of Β1 B integrin isoform in caspase-8-dependent integrin-mediated keratinocyte death. / Lotti, Roberta; Marconi, Alessandra; Truzzi, Francesca; Dallaglio, Katiuscia; Gemelli, Claudia; Borroni, Riccardo G.; Palazzo, Elisabetta; Pincelli, Carlo.

In: Journal of Investigative Dermatology, Vol. 130, No. 11, 11.2010, p. 2569-2577.

Research output: Contribution to journalArticle

Lotti, Roberta ; Marconi, Alessandra ; Truzzi, Francesca ; Dallaglio, Katiuscia ; Gemelli, Claudia ; Borroni, Riccardo G. ; Palazzo, Elisabetta ; Pincelli, Carlo. / A previously unreported function of Β1 B integrin isoform in caspase-8-dependent integrin-mediated keratinocyte death. In: Journal of Investigative Dermatology. 2010 ; Vol. 130, No. 11. pp. 2569-2577.
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