For Dr. Janis Burt’s physiology research group at the University of Arizona, these are just some of the big-picture questions driving the lab’s focus towards understanding how connexin proteins regulate and are regulated by the cells of blood vessels.
It’s important to our health that our blood vessels grow the right way; that they get to body parts that need blood, that they heal after damage, and that they don’t grow to feed tumor cells. To make sure vessels grow correctly, connexin proteins form channels, or connections, between cells.
These connections allow cells to “talk” to each other, to share information and act simultaneously- it’s like talking to your neighbor through the gaps in your shared fence and making plans together. In the blood vessels, cells use connexins to talk and coordinate when they’ll grow, when they’ll stop growing, or even when they’ll die.
The question is, what makes cells choose growth or death? To extend the fence analogy, there are a lot of things that could change how you talk to your neighbor through the fence. Perhaps there are several gaps in a short fence, and you are speaking loudly; or maybe there are few small holes, the fence is tall, you’ve lost your voice and can barely whisper. There can be many variations.
The same is true of how cells use connexins; changes can make cells talk more, or talk less, discuss different topics, in a loud voice, or in a quiet voice, and so on. There are many ways they can communicate, and the way they talk to each other (or don’t talk) influences whether cells in blood vessels grow, stop growing, or die. In turn, that can influence how well blood vessels heal after an injury, or if they’ll stop growing towards a tumor that demands nutrients from blood.
The Burt lab is currently looking at two of the many factors that affect connexin function. One way of changing connexin function is to control how well the connexin proteins get to the membrane- in this metaphor, the fence. Maybe your neighbor cannot walk by himself very well, and needs his grandson to take his arm and walk him over. In the same way, small pieces of connexins can chaperone complete connexins to the membrane. These small pieces are known as truncated isoforms, and they can change or enhance the messages cells are sending to each other.
Another way to change connexin function is by phosphorylation, which is a little like adding decorations to the protein. Depending on where the “decoration” is placed on the connexin can change how cells talk to each other. With decorations placed one way, they might say “let’s all proliferate,” and the cells will grow together. But with a different decorative design, they might say to each other “let’s all go into apoptosis,” which is a controlled and normal method by which cells die.
The Burt lab is working on understanding these changes. Where is phosphorylation happening? How do truncated isoforms work? How do such changes to connexins cause cells to communicate differently? How does altered cell chatter make cells grow or die?
Understanding the basic science is the first step towards using discoveries for treatments and prevention. There are more questions than answers right now, but one day we could be using our deeper understanding of connexins for things like ultra-fast healing, impeccable artificial blood vessels, or starving tumor cells of nutrients.
UA Department of Physiology
Dr. Janis Burt
UA Department of Physiology