CoachApoptosis is programmed cell death by an intrinsic sequence: the cell shrinks and rounds up, its chromatin condenses and its DNA is cut between nucleosomes into a ladder of fragments, the nucleus breaks up, the membrane blebs into sealed vesicles, phosphatidylserine appears on the outer face of the membrane as an “eat me” signal, and the fragments are engulfed by neighbours or macrophages within an hour — without leakage, and therefore without inflammation. It is executed by caspases, cysteine proteases that cut after aspartate, made as inactive zymogens: initiator caspases (8 and 9) are activated by being brought together on a platform, and they cleave and activate the executioner caspases (3 and 7), which cut several hundred substrates — the lamins, the cytoskeleton, the inhibitor of the DNA-cutting nuclease, the enzyme that keeps phosphatidylserine inside. Necrosis, by contrast, is death by injury: the cell swells, bursts, spills its contents and provokes inflammation. Apoptosis was named and its morphology described by Kerr, Wyllie and Currie (1972); its genes were found in a worm.
Examples
Example 10.10 (Deaths that build a body)
The fingers are carved from a paddle by the apoptosis of the cells between them; in the duck the same cells live and the webbing stays. The tadpole’s tail is resorbed at metamorphosis on the signal of thyroid hormone. About half of the neurons produced in the vertebrate nervous system die before birth, those that fail to receive enough trophic factor from their targets — a competition that matches the number of neurons to the size of the field they serve. Ninety-five per cent of the T cells made in the thymus die there, selected away because they recognise nothing or recognise the self (Chapter 16). And every day the intestinal epithelium sheds its oldest cells at the villus tips, the skin its keratinocytes, the blood its aged neutrophils after a life of a day: apoptosis is the routine, and the tissue’s size is the difference between two large rates.