The Outer Trigger

Okay, so you've got your caspase bomb. But before the Alien lays any more eggs or the Klingons take the ship, you'll need a trigger to set it off.

There are two ways to trigger apoptosis. Both involve the participation of death domains, which are regions inside involved proteins that like to bind to other death-domains.

In Extrinsic Apoptosis, a cytokine, such as Tumor Necrosis Factor (TNF) or Fas, binds to a cell-surface receptor, and initiates the cell-suicide processes by causing the intracellular part of the receptor to expose a death domain. This, as we shall see, recruits other death-domain-containing proteins to the receptor, which activates those proteins and initiates the cascade. Some people think this receptor doesn't play much of a role in global brain ischemia, but may be more important in focal brain ischemia, wreaking havoc in the penumbra. In the animation below, note how binding of the cytokine to its receptor exposes death doman, recruiting an initiatior caspase (caspase 8), which in turn cleaves executioners (caspase 3 et al) and activates a caspase cascade.

Animation. Extrinsic apoptosis couples ligand binding to cell-surface receptors with intracellular caspase activation and all the wickedness that follows.