| Endothelial type I interferon signaling modulates the vascular response to ischemic brain injury |
Kavli Affiliate: Shai Shaham
| Authors: Olya Yarychkivska, Lena M Kutscher, Dana Mamriev, Betty Ortiz Bido, Yun Lu, Wolfgang Keil, Sarit Larisch and Shai Shaham
| Summary:
Nuclear degradation accompanies cell death. To study this process, we followed nuclear dismantling of the C. elegans linker cell, which undergoes a non-apoptotic morphologically-conserved death program characterized by nuclear envelope crenellations and cell splitting. We show that although linker cell death is cell autonomous, nucleus elimination follows engulfment and is blocked in rab-35 and arf-6 phagosome maturation mutants. Surprisingly, although linker cell death is independent of the apoptotic caspase CED-3, CED-3 is partially required within the linker cell, and upstream of RAB-35 and ARF-6, for cell splitting, engulfment, and nucleus elimination. In parallel studies, we found that the kinase inhibitor staurosporine causes mouse embryonic fibroblasts to undergo caspase-independent non-apoptotic death accompanied by nuclear crenellations and, paradoxically, by Caspase-3 activation. Our findings suggest mechanistic similarities between staurosporine-induced and linker cell death, revealing that, in some contexts, caspases do not initiate cell death but instead promote subcellular tasks required for cell clearance.