G protein-coupled receptor oligomers, or GPCR, had already proposed to play critical roles in cell signaling by sensing molecules outside the cell and signaling cellular responses. Only they hadn’t been confirmed in native tissues until now.
Dr. Maurice Manning, UT Distinguished University Professor in the Department of Biochemistry and Cancer Biology, and UT research associate Stoytcho Stoev provided the key ligand binding molecules needed for the study, “Time-Resolved FRET Between GPCR Ligands Reveals Oligomers in Native Tissues.”
The study, representing the multiyear work of a 19-member research team, recently was published in Nature Chemical Biology. The research was led by Drs. Thierry Durroux, Bernard Mouillac, and Jean-Philippe Pin of the Institut de Genomique Fonctionnelle in Montpellier, France.
Nearly all of the ligands used in this study came from Manning and most have been characterized for this work through longtime collaboration between their laboratories, Durroux said.
“A large part of the success is linked to the quality of the collaboration in which the personality of Dr. Maurice Manning, his scientific skills, and his capacity to adapt to our requests have been crucial,” he said.
Manning’s lab has been a leader in the field of designing peptide ligands, agonists and antagonists for the four different receptors for the peptide hormones Oxytocin and Vasopressin. Over the years, he has provided samples of these peptides to other scientists in the United States and worldwide for their independent studies.
He has been collaborating with researchers in Montpellier, France, for more than 30 years and was happy to contribute to this research, he said.
“It’s a very exciting study. I have to take my hat off to the leaders of this study for their persistence in having these exciting findings published in such a highly prestigious journal,” Manning said. “It sets up a whole new paradigm for how molecules interact with their receptors in native tissues. It could provide fresh insights into therapies for a variety of diseases.”
The GPCR had been demonstrated in cells in a lab environment, but not in real tissue as was the case with this study, Manning said.
The researchers used a time-resolved fluorescence resonance energy transfer strategy to detect activity of receptors with selective fluorescent ligands.
The theory was first applied to a set of cells known to react with peptide ligands and was then applied for the first time to native tissues, specifically mammary gland tissue. The research succeeded in demonstrating the presence of the dimeric receptors for Oxytocin.