“Language” Of The Cells Decoded by the Researcher
The bone morphogenetic protein (BMP) signaling pathway comprises multiple ligands and receptors that interact promiscuously with one another and typically appear in combinations.
And now, a research team from Caltech has uncovered the molecular code that cells use to communicate with each other, using this very pathway.
Can you imagine what it would be like if your brain couldn’t tell your leg muscles to contract so you could walk? Or what if you had contracted an infection and your immune system had to deal with it? Cells need to be able to communicate with each other to do these things, and so much more!
Therefore, to understand this “language” the cells use, Caltech scientists studied a major communication channel, called the bone morphogenetic protein (BMP) pathway that operates in nearly all tissues and is a target for cancer therapies.
Just as humans use letters and words to create messages, cells release molecules called ligands into the environment to send messages to their neighbors—such as an instruction to differentiate or proliferate. The ligands bind to receptors on the surface of other cells, which interpret the message and trigger a set of chemical reactions to relay it to
the correct molecules in the cell’s interior.The BMP pathway uses many different ligands and receptors in various combinations. Oddly, the ligands and receptors in this pathway were found to mix and match with each other in many different ways seemingly for no reason.
“You might think each type of ligand would pair up with only one type of receptor, but this isn’t the case,” says Michael Elowitz, professor of biology and bioengineering at Caltech and an investigator with the Howard Hughes Medical Institute. “Instead, all of the ligands interact promiscuously with all of the receptors. It seems like a big mess, and quite different from the way people design communication systems to keep each communication channel separate. So we wondered why cells communicate in this way.”
In order to figure out what benefit molecular promiscuity provides, the team created different mixtures of BMP ligands in the laboratory and added them to certain cells: breast cells, embryonic stem cells, and connective tissue cells called fibroblasts, all from mice.
“One day, I came to the lab and mixed two ligands together that, each on their own, activate cells very strongly,” says Yaron Antebi, a Caltech postdoctoral scholar in biology and biological engineering. “But when I checked the cells the next day, there was no response at all. This led us to theorize that cells aren’t listening to individual ligands, but rather to combinations of ligands. It’s the combinations that are meaningful. Different combinations of ligands encode different instructions for the cell.”
“We were amazed to find that there is not only one kind of information encoded in these ligands,” says James Linton, a research scientist in the Elowitz lab. “Different cells can extract different messages, such as instructions to proliferate or differentiate, from the same molecules.”
The group found that this ability to encode multiple messages using the same molecules arises because distinct cell types express different combinations of receptors on their surfaces. One feature of this communication system is the ability for cells to address messages to specific cell types.
The researchers believe their study provides a foundation for understanding how information is distributed across molecules, on which further studies could be based on to elucidate novel biological drugs that could target tumors or particular cell types without affecting any other cells.
