A University of Toledo chemistry and biochemistry faculty member and his research team of graduate students have answered a fundamental biological question about cell migration that could have implications for enhanced medical treatments.
Results from the two-year study have been published in the Oct. 20 issue of the Journal of Biological Chemistry.“If we better understand how cells migrate, we can target some of these molecules for therapeutic purposes,” said Dr. Ajith Karunarathne, assistant professor in the Department of Chemistry and Biochemistry, who led the research team.
Scientists have long been trying to better understand exactly how cells move throughout the body. If you can control a cell’s movement, you might be able to prevent cancer cell movement and secondary tumor formation in vital body organs such as the lungs or pancreas. Or you could help immune cells move to the site of an infection and accelerate healing.
In their research, the UT team targeted the cell’s G protein-coupled receptors, or GPCRs. These receptors are known as the “sniffers,” Karunarathne said, because they sense the environment and steer the cell where it’s needed in the body. They also regulate everything from heart rate to how much insulin the pancreas kicks out.
One-third of marketed drugs are used to control the GPCR pathways, according to Karunarathne. That includes everything from beta blockers to cancer and diabetes medicines.
When a cell moves, the front of the cell scoots forward, while the back of the cell retracts. You need both things to happen for the cell to move. It’s called “treadmilling.” Until now, scientists haven’t had much information on the how the retraction piece of the puzzle works, Karunarathne said.
In its study, the research team inserted GPCR receptors from the eye, which are sensitive to light, into cells from other parts of the body. They then used light to activate the receptors and target a specific area in the front of the cell. In this way, they could take a look at how the back of the cell reacted — the piece of the puzzle that’s been missing.
The use of light receptors was an important innovation in the team’s research. It is part of a fairly new field called subcellular optogenetics, Karunarathne said.
Normally, chemicals are used to activate receptors. But chemicals, which dissipate throughout the cell, are hard to control. By using light instead to stimulate the receptors, researchers could target specific, small regions on a single cell. They also could turn the light on and off, stopping and starting the activation.
As the researchers activated the GPCR in the front of the cell, the cell generated proteins. Through trial and error, and by targeting combinations of those proteins, the UT team found two pathways that affect how the back of the cell retracts and that are essential to cell migration. Stop either of those pathways and the cells can’t move.
With this discovery, scientists can now begin thinking about how to create therapies that either slow, stop or accelerate a cell’s movement. Karunarathne said one possibility is gene therapy whereby patients are injected with genes that make cells to produce light-sensitive GPCRs. Tumor cells could be “told” not to migrate, and immune cells could be “told” to attack nasty infections.