A just-published study out of the Stanford University School of Medicine has found that the apoptotic control network includes several positive feedback loops that may allow apoptosis to spread through the cytoplasm in self-regenerating trigger waves.
It's not the first time trigger waves have been identified in the microcosms of life. The cell cycle, a cornerstone of cell biology, regulates production via trigger waves, too. So do neuronal action potentials, which allow neurons to pass signals via electrical impulse.
"This work is another example of how nature makes use of these trigger—things that most biologists have never heard of—over and over again," said James Ferrell, M.D., Ph.D., professor of chemical and systems biology and of biochemistry. "It is a recurring theme in cell regulation. I bet we'll start to see it in textbooks soon." The study was published in Science today.
Trigger waves require two main elements: a positive feedback loop and a threshold think—falling dominoes. Trigger waves in an apoptotic cell are governed by that same phenomenon. Once cell death is initiated, by way of disease or something else, specific killer proteins in the cell, called caspases, activate. These proteins then float to other caspases and activate them; those follow suit until the entire cell has to pack it in.
"It spreads in this fashion and never slows down, never peters out," Ferrell said. "It doesn't get any lower in amplitude because every step of the way it's generating its own impetus by converting more inactive molecules to active molecules, until apoptosis has spread to every nook and cranny of the cell."
So far, apoptosis is the only form of cell death in which trigger waves have been identified, but Ferrell is investigating other processes in biology to see if the continual waves might play a role.
Now, they're looking into whether trigger waves might be responsible for how our innate immune response spreads from cell to cell. Viruses spread from cell to cell through trigger waves, so it makes sense that our initial line of immune defense might employ the same tactic.
"We have all this information on proteins and genes in all sorts of organisms, and we're trying to understand what the recurring themes are," Ferrell said. "We show that long-range communication can be accomplished by trigger waves, which depend on things like positive feedback loops, thresholds and spatial coupling mechanisms. These ingredients are present all over the place in biological regulation. Now we want to know where else trigger waves are found."