Cells in the human body communicate with one another for many different reasons, including to help organs develop correctly and to produce a healthy response to injury and infection. Signalling proteins, such as growth factors and cytokines, form the main language of this communication.
Initially, many growth factors and cytokines remain attached to the surface of the cell that made them. When cells need to send a message to another one, an enzyme called ADAM17 acts like a pair of scissors to release the proteins from the cell surface, allowing them to travel towards other cells. This process must be carefully controlled because releasing too many growth factors or cytokines (or releasing them at inappropriate times) can lead to cancer and inflammatory diseases such as rheumatoid arthritis.
Another group of proteins called iRhoms bind to ADAM17 to regulate the enzyme’s activity. But what controls the activity of the iRhom proteins themselves? To find out, Künzel et al. used a technique called a proteomic screen that can identify which proteins bind to each other. This revealed that a protein called FRMD8 binds to iRhoms. Further experiments in human cells and mice revealed that FRMD8 maintains adequate levels of both ADAM17 and iRhoms at the surface of the cell. Cells that lack FRMD8 break down ADAM17 and iRhom proteins and release fewer growth factors and cytokines.
Further work could help us to learn whether stopping FRMD8 from interacting with iRhoms could reduce cell communication. This, in turn, might reduce inflammation or cell growth. If so, then developing drugs that prevent FRMD8 from binding to iRhoms could lead to new treatments for inflammatory diseases and cancer.
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