Scientists at the Wertheim UF Scripps Institute for Biomedical Innovation & Technology have discovered that the amino acid glycine can send a “slow-down” signal to the brain, potentially contributing to major depression, anxiety, and other mood disorders. The findings, published in the journal Science, could help develop new, faster-acting medications for such conditions.
A model shows how glycine molecules interact with brain cell receptors called GPR158 to influence the nervous system. The dotted lines show hydrogen bonds and weak electrical field attractions that start the signal. Credit: Courtesy of the Martemyanov lab, The Wertheim UF Scripps Institute. That offered strong evidence that GPR158 could be a therapeutic target, he said. But what sent the signal?. What they saw surprised them. The GPR158 receptor looked like a microscopic clamp with a compartment — akin to something they had seen in bacteria, not human cells.“We were barking up the completely wrong tree before we saw the structure,” Martemyanov said. “We said, ‘Wow, that’s an amino acid receptor. There are only 20, so we screened them right away and only one fit perfectly.
“Usually receptors like GPR158, known as G protein Coupled Receptors, bind G proteins. This receptor was binding an RGS protein, which is a protein that has the opposite effect of activation,” said Thibaut Laboute, Ph.D., a postdoctoral researcher from Martemyanov’s group and first author of the study.
“An orphan receptor is a challenge. You want to figure out how it works,” Laboute said. “What makes me really excited about this discovery is that it may be important for people’s lives. That’s what gets me up in the morning.”