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

en macrophages phagocytosed special beads carrying pieces of germs, there was a rapid movement of the autophagy-associated LC3 proteins to the developing phagosome. The scientists then fed particles called zymosan (killed yeast cells) to macrophages that lacked TLR. In those macrophages, the movement of LC3 to phagosomes in response to zymosan ingestion was significantly slowed. This suggested that TLR was required for triggering movement of LC3 to the phagosome, Green said.

The team also showed that two proteins critical for autophagy, ATG5 and ATG7, were key to the ability of macrophages to enable phagosomes to mature. For example, macrophages lacking ATG5 were not able to fuse phagosomes with lysosomes. While macrophages lacking ATG7 were able to phagocytize live yeast cells, the yeast were more likely to survive degradation in macrophages without ATG7 than yeast ingested by normal macrophages. This indicated that ATG7, a protein scientists thought was exclusively associated with autophagy, also participates in the destruction of pathogens internalized by phagocytosis.

This strongly suggested that TLR recruits parts of the autophagy machinery to enable the phagosome to fully develop and fuse with the lysosome even if autophagy itself doesnt occur simultaneously, Green said.

We can actually see phagocytosis take place in live cells and we can study it in detail, so we know the steps involved, said Miguel Sanjuan, Ph.D., a staff scientist in Greens laboratory. But autophagy seems to occur suddenly and we know about it only after its very obviously underway. Now that we discovered that phagocytosis uses some of the same biochemical signals as autophagy does, we can use that information to solve the mystery of how autophagy works. We hope that we will be able to translate that new knowledge in the future into improved treatments for infections and cancer.


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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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