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Dec 20, 2007

Scientists Find Link between Cellular Defense Processes Inside and Outside Cells

  • A team from St. Jude Children's Research Hospital say that macrophages use proteins invovled in autophagy for phagocytosis.

    The processes of phagocytosis and autophagy enclose various cellular structures or germs within a sac that fuses with a bag of digestive enzymes called the lysosome. Scientists already knew that a critical step in autophagy is the binding of many molecules of the protein LC3 into clumps and that certain phagocytes called macrophages 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. Previous research found that TLR also triggered autophagy.

    The St. Jude team showed that when 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 was significantly slowed.

    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 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 doesn’t occur simultaneously,” explains Douglas Green, Ph.D., chair of the St. Jude department of immunology and the paper’s senior author.

    A report on the discovery appears in the December 20 issue of Nature.



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