Researchers at the University of Toronto in Canada have uncovered an immune mechanism by which host cells combat bacterial infection, and, at the same time, found that a protein crucial to that process can sense and respond to misfolded proteins in all mammalian cells. The protein is called heme-regulated inhibitor (HRI), and the researchers showed that during bacterial infection it triggers and coordinates a chain reaction among other proteins that form a larger complex. That larger group or “signalosome” amplifies inflammation and leads to an anti-bacterial response. But HRI can also regulate protein folding in other cell types, the researchers showed. Protein folding, which helps determine the 3-D shape of a protein and is essential for its function, is implicated in non-infectious diseases including the neurodegenerative disorders Parkinson's, Alzheimer's, and ALS. "The innate immune function that we discovered is essentially a mechanism of protein scaffolding, which is important because you want a quick and orderly response to bacterial infection," says Stephen Girardin (photo), PhD, a Professor of Laboratory Medicine and Pathobiology and of Immunology at th U of Toronto. "But we also found that same pathway is important for protein scaffolding and aggregation in other cells, which opens promising research angles for neurodegenerative and other diseases." The findings were published online in Science nline on July 5, 2019. The article is titled “The Heme-Regulated Inhibitor Is a Cytosolic Sensor Of Protein Misfolding That Controls Innate Immune Signaling.” Researchers have studied HRI for over three decades, but mostly in the context of red blood cell disorders.
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