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 language | English |
|---|---|
| Pages (from-to) | 2569-2577 |
| Number of pages | 9 |
| Journal | Journal of Investigative Dermatology |
| Volume | 130 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2010 |
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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 journal › Article
}
TY - JOUR
T1 - A previously unreported function of Β1 B integrin isoform in caspase-8-dependent integrin-mediated keratinocyte death
AU - Lotti, Roberta
AU - Marconi, Alessandra
AU - Truzzi, Francesca
AU - Dallaglio, Katiuscia
AU - Gemelli, Claudia
AU - Borroni, Riccardo G.
AU - Palazzo, Elisabetta
AU - Pincelli, Carlo
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77957935569&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957935569&partnerID=8YFLogxK
U2 - 10.1038/jid.2010.195
DO - 10.1038/jid.2010.195
M3 - Article
C2 - 20613771
AN - SCOPUS:77957935569
VL - 130
SP - 2569
EP - 2577
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 11
ER -