The competitive protein battle royale within your cells
January 20, 2020
Picture a cell. You probably picture a small, harmonious system that’s working together to survive on its own like bacteria, or as part of a larger organ or body system like your own cells. You probably don’t picture a system where different parts of the cell are competing with one another, fighting for a location or ability to perform a function, do you?
Despite your imagined image of a cell, a major part of what drives the systems in your cells to do what they need to do, at the right place and the right time, is a constant battle royale of competing parts.
My research in Dr. David Kovar’s laboratory focuses on how two cellular components can either compete or cooperate together to stake out an area in the cell for a specific function. Specifically, I work on something called the actin cytoskeleton, the most abundant protein in the cells of eukaryotes (mostly animals, plants and fungi) that link together to form large networks to carry out a wide range of tasks inside the cell, ranging from helping cells take in nutrients to dividing and even helping cells to crawl. These networks are dynamic, constantly assembling and disassembling, while using different proteins to help perform each task at a specific time and place.
Once we understand these smaller processes ... it will teach us how a cell can manage so many different tasks in perfect harmony.
Because the actin cytoskeleton performs so many different roles in the cell, it’s important to understand how the proteins for a specific task will attach only to the right actin network. If a cell needs protein A for nutrient uptake, we wouldn’t want it to be working with the actin network that helps cells divide. If that happens, it could lead to the halting or speeding up cell division, a resulting factor in diseases such as cancer where cell growth becomes unregulated. So, how can a cell make sure protein A only goes where it is supposed to and does not end up in the wrong place?
This is where the competition comes in. One way in which cells can make sure protein A only associates with the right network is by putting another protein there first. This is known as competitive inhibition: if protein B binds first, it could physically prevent protein A from being there, or B could change the actin network in some other way so A can no longer bind. Instead, all of A will now have to localize to whatever actin network is available, putting it at its proper place in the cell.
Disassembly, competition and cooperation
My research focuses on how proteins that disassemble actin networks compete with other proteins. Disassembly is a huge component for actin networks to perform jobs within a cell. For instance, in cell division, some cells need to form a ring of actin that constricts the middle of the cell to split it into two equal parts. To do this, the actin network must 1) assemble a large ring and then 2) make this ring smaller and smaller in order to constrict. Part of this process of the ring getting smaller is done by disassembling the network. Without disassembly, the cells would have a large ring-like actin network, but no way to separate the single cell into two cells and divide, so understanding the proteins that help with this disassembly process is important for us to understand how cell division occurs.
Specifically, we purify all these components by using beads coated with specific chemicals or proteins to which only our protein of interest can bind. This allows us to separate one type of protein from the whole cells. That way we can look at individual proteins and how they interact with actin networks both alone and together without worrying about other factors. To do this we use Total Internal Reflection Fluorescence Microscopy, an imaging technology that lets us see a single molecule of protein on an actin filament. We label these proteins with fluorescent molecules which let us see how their interactions with actin networks change when another protein is present. The idea is that the presence of these other proteins will either help or prevent actin network disassembly due to competition or cooperation with one another.
By looking at these component systems in isolation, I hope to be able to discover small details that will allow us to see the bigger picture: How does disassembly factor into cell division or a cell’s ability to move? Do other proteins compete to prevent disassembly from occurring? Once we understand these smaller processes, whether they be competitive or cooperative, it will teach us how a cell can manage so many different tasks in perfect harmony. Then, we may be able to understand how and when these systems go awry in diseases such as cancer, where the cells’ ability to move or divide quickly greatly influence both tumor growth and the spread of cancer. In the meantime, the next time you picture a cell, remember that the competition rages on.