Apoptosis in Caenorhabditis elegans

In cells that receive a death signal, the caspase enzyme CED-3 is activated and directs morphological changes in the dying cell. This occurs through cleavage of key substrates, which (although not yet identified in worms) are likely to fall into two camps: 'swords' and 'shields'. Swords are activated by cleavage and promote apoptosis; examples in mammals include ICAD–CAD, which cuts DNA. Shields support normal cellular functions until they are cleaved and inactivated; mammalian examples are poly-ADP-ribose polymerase and DNA-PK, both of which are involved in DNA repair. The substrates that produce the 'eat-me' signal are presumably the most active or most easily activated, as engulfment of apoptotic cells by phagocytes prevents or obscures recovery from the other stages. Phagocytes that bind to cells displaying 'eat-me' markers deliver a signal that enhances apoptosis. The signals that result in cytosolic shrinkage ('shrink me'), leading to the ring stage, or loss of nuclear–cytosol distinction ('blend me'), leading to the erythrocyte stage, are presumably reversible. The 'crush-me' events that lead to the lentil stage may not be reversible. IAP, inhibitor-of-apoptosis protein.