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St. Jude finds link between cellular defense processes, showing how cancer cells survive
Date:12/19/2007

sac called the phagosome.

Autophagy destroys germs that have already forced their way into the cell; isolates and breaks down defective molecules in the cell; destroys structures in the cell that normally carry on important biochemical processes but then begin to produce toxic wastes; and breaks down large molecules to obtain nutrients during times of stress or to obtain building blocks for specific new molecules the cell needs.

Immune system cells called phagocytes use phagocytosis for the outside job of environmental cleanup, engulfing germs by trapping them within a depression that forms in the cells surface. The open end of the depression then closes and the newly formed sac moves to the inside of the cell where it fuses with the lysosome.

The researchers based their study on the findings of previous research that demonstrated specific signals associated with both autophagy and phagocytosis. Scientists already knew that a critical step in autophagy is the binding of many molecules of the protein called LC3 into clumps. Certain phagocytes called macrophages that are on the prowl for germs use the TLR proteins on their surface to sense the presence of their prey. When the macrophage engulfs a germ and forms the depression that traps the microbe, TLR triggers a series of biochemical events that guide development of the phagosome. However, previous research found that TLR also triggered autophagy.

We suspected that because TLR signaling triggers both phagocytosis and autophagy that this signal might also link these activities together as well as enable each process to occur separately, Green said. This would make sense, since autophagy kills microorganisms that invade the cell and phagocytosis deliberately brings microorganisms into the cell to destroy them. So having two totally separate and unrelated sets of signals to do a similar job would be like re-inventing the biochemical wheel.

The St. Jude team showed that wh
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Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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