Research on cell communication may help cure neurodevelopmental disorders

April 8, 2019

In the human body, trillions of cells constantly gather information from one another, make collective decisions, and move together—they don’t just behave by themselves. But how exactly do cells communicate with one another? 

This question is at the core of Demet Araç’s research. An assistant professor in the University of Chicago’s Department of Biochemistry and Molecular Biology and the College, Araç works with important signaling molecules located on the cell membrane called G-protein-coupled receptors (GPCRs). These receptors use proteins to communicate with each other, especially during the cell development process.

“The receptors adhere to each other, which is one way of communicating,” Araç explained. “Mechanical force, in terms of movement, may be another part of the signal these receptors are sensing. By touching each other, they give a signal to each protein which is then transmitted into the cell. Then each cell makes decisions based on those signals. All cells in our bodies do this.”

Araç wants to determine how this communication process connects to intracellular signals. Many diseases are caused by a problem in this process, and even broken or modified communication among cells can result in diseases such as autism, attention-deficit hyperactivity disorder (ADHD), cancer, brain modifications, and other various neurodevelopmental disorders. Araç’s research primarily focuses on a subfamily of receptors known as adhesion-type GPCRs. While this subfamily is one of the largest receptor groups of its kind, little is known about how it works, although it is thought to play a key role in brain functionality. 

As a postdoctoral fellow at Stanford University, Araç discovered a previously unknown domain that exists in all adhesion-type GPCRs known as the GPCR autoproteolysis inducing (GAIN) domain. Her work at UChicago continues focusing on understanding the basic scientific functionality of adhesion-type GPCRs and how they impact brain activity. By using cells from mice and zebrafish, Araç and her team conduct test-tube research and deliberately create mutations to disrupt cell functionality. They then determine whether the disruption is critical to normal cell development. 

“We look at 3D atomic structures to give us a molecular picture of the receptors in very high resolution to see how they bind to each other. We can see actual atoms on these pictures,” Araç said.  

Ultimately, this research could result in the creation of new drugs that would adhere to the proteins, correct malfunctioning, and cure diseases. Araç is also working with different proteins that affect other systems of the body in similar ways. In 2018, she was the lead researcher on a paper published in Cell that identified a human protein in the brain which aids in cellular communication that resembles a bacterial toxin.

“Before we saw the structure, we didn’t know the origin of the protein and realized that the structure is very unique and is similar to one toxin that forms from bacteria and doesn’t look like any other protein. It evolved from a bacterial toxin, and it’s in our brain, which is very weird. Why is something in our brain so similar to a bacterial toxin? We’re now trying to understand that,” Araç said.

Because research on these newly discovered protein receptors is still in early stages, synthetic testing in humans is still many years away. Araç remains focused on determining what other important biological functions these proteins are tied to.

“These are very large and complex structures and are quite difficult to understand, but the impact they have in overall cell communication is huge, and they may play other roles in development that have yet to be discovered,” she said.