Proteomics study yields clues as to how tuberculosis might be thwarting the imm...( BERKELEY CA -- A link between the im...)

BERKELEY, CA -- A link between the immune system and the self-cleaning system by which biological cells rid themselves of obsolete or toxic parts may one day yield new weapons in the fight against tuberculosis and other deadly infectious diseases. Scientists with the U.S. Department of Energy's (DOE) Lawrence Berkeley National Laboratory (Berkeley Lab) have discovered proteins residing in both systems that point to "cross-talk" between them.

In a collaboration between the research groups of Carolyn Bertozzi, director of Berkeley Lab's Molecular Foundry nanoscience center, and Jay Keasling, director of Berkeley Lab's Physical Biosciences Division, profiles were obtained for 546 different types of proteins in the membrane of a phagosome, an organelle of macrophages (a type of white blood cell) that essentially "eats" and destroys invading organisms (a process called phagocytosis). This represents the most comprehensive proteomic analysis of a phagosomal membrane to date.

"We were able to identify many new proteins that were not previously known to reside in the phagosome," said Wenqing Shui, a member of both the Bertozzi and Keasling research groups, and a proteomics specialist who was the lead author on a paper reporting these results in the Proceedings of the National Academy of Sciences.

"One of the new proteins exclusively found in our study, LC3-II, is considered a marker of autophagy, the process that enables cells to clean up their own cytoplasm," Shui said. "Not only was LC3-II present in the phagosome, its level was increased upon the induction of autophagy in macrophages, and reduced when autophagy was suppressed. This indicates cross-talking between autophagy and phagocytosis that may play an important role in the response of the immune system."

The PNAS paper is entitled: "Membrane proteomics of phagosomes suggests a connection to autophagy." Co-authoring this paper in addition to Shui, Berto
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