Splicing to Save Memory

Part of any cell’s life is its death. There are several cell death pathways that are activated by different stimuli and carried out by a range of cellular effectors. Three common cell death pathways are apoptosis, necroptosis and pyroptosis. Understanding the intricacies of distinct mechanisms of cell death is the basis to understanding a wide variety of human health issues from normal or abnormal immunological responses to pathogenic infections and aging. Caspases are a family of cysteine-dependent aspartate-directed proteases that mediate many cell death decisions. Although the basic function of the caspase family has been known for decades, researchers continue to work out the complexities of cell death decisions.

Caspase 8 is one member of the caspase family. Recently, by studying the function of a catalytically inactive mutant, a scaffolding function of caspase 8 was identified. However, the importance of its scaffolding function in different contexts is not known. Two recent papers in Nature examined the scaffolding function of caspase 8 in mammalian development, specifically in embryonic mouse development (1, 2). One of these papers, Fritsch et al., genetically engineered a mouse to express only the catalytically inactive form of caspase 8 (Casp8(C362S)) through CRISPR-Cas9 editing of mouse zygotes...