Study Shows Humans and Plants Share Common Regulatory Pathway

Research Could Shine New Light on Human Immune Response to Infection

13-Apr-2007

In findings that some might find reminiscent of science fiction, scientists at The Scripps Research Institute have shown for the first time that humans and plants share a common pathogen recognition pathway as part of their innate immune systems. The data could help shed fresh light on how pathogen recognition proteins function and the role they play in certain chronic inflammatory diseases.

The study provides new evidence that Nod1, a member of the Nod-like Receptor (NLR) protein family, is activated by the protein SGT1, which also activates Resistance (R) proteins in plants; R proteins protect plants from various pathogens. The study also confirms structural similarities between the Nod1 protein, which plays a pivotal role in the innate immune system's recognition and response to bacterial infection and members of the R protein family.

"There has been a great deal of speculation that R proteins and Nod1 are related, but our study provides the first direct link between plants and humans," said Richard Ulevitch, the Scripps Research scientist whose laboratory conducted the study. "Plants have Nod-like receptors and similar immune responses to bacteria and other pathogens - the R proteins evolved to counteract these pathogenic effects. Our study provides a new perspective on the Nod1 pathway in mammalian cells as well as the value of drawing on plant studies of R protein pathways to better understand the pathogen recognition functions of these proteins."

The Nod proteins recognize invasive bacteria, specifically distinct substructures found in Gram-negative and Gram-positive organisms. Once activated, Nod1 produces a number of responses that include activation of intracellular signaling pathways, cytokine production and apoptosis or programmed cell death. Despite the fact that various models of Nod1 activation have been described, little has been known about other proteins that might affect the protein's activation. In contrast, a number of additional proteins have been linked to the activation pathways of the R protein in plants.

"The NLR family has clear links to human disease," Ulevitch said. "Out of the more than 20 proteins in the NLR family, several mutations are linked to diseases that involve chronic inflammation or autoimmune consequences. Up to now, there has been a limited understanding of the regulatory pathways of Nod1. By identifying SGT1 as a positive regulatory protein, our study offers new insights into the entire family."

SGT1 is a protein found in yeasts, plants, and mammals in both the nucleus and the cytosol. It functions in several biological processes through interaction with different multi-protein complexes. A large body of evidence also suggests that the protein plays a role in regulating pathogen resistance in plants. Various genetic studies have identified SGT1 as a crucial component for pathogen resistance in plants through regulation of expression and activities of some R proteins

Although there is a significant genetic crossover between plants and mammals, very little is known about this common human-plant regulatory pathway. Ulevitch speculated that certain protein regulatory structures might exist in both plants and humans simply because they do the same thing in much the same way.

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