Research groups are investigating the collaborative functioning of proteins that allow our cells to adhere as well as move. A key focus of their studies is the protein, paxillin.
Tissues in our body can only remain intact if the cells not only stick to each other but also connect to extracellular components, like the collagen fibers found in connective tissue and skin. But how does this process occur at the cellular level? What roles do the various proteins play? Recent data and discoveries have been published by research teams led by cell biologist Christof Hauck from Konstanz, Germany, and chemist Heiko Möller from Potsdam, Germany, in the open-access journal PLOS Biology. The outcomes of their research could help advance medical treatments already in use for conditions such as inflammatory bowel diseases or in the prevention of heart attacks.
Paxillin: A Link to the Cell’s Support System
Specialized membrane proteins known as integrins play a crucial role in holding tissues together. They serve as attachment points for cells. Each cell possesses numerous anchoring points called focal adhesions, which provide the cell with stability akin to little feet. For integrins to connect with the cytoskeleton, the cell’s internal support system, they must interact with other proteins.
Paxillin is one of these proteins. Found in all cells, it connects integrins to the cytoskeleton and acts as a visual marker for the dot-like and line-like anchoring points, known as focal adhesions.
Despite the implications of the terms ‘cytoskeleton’ and ‘focal adhesion,’ these anchoring sites are not static. For instance, during cell movement, they are continuously formed and broken down, such as when connective tissue cells work to heal a wound in the skin. Recent data indicate that paxillin attaches directly to the intracellular portion of integrin, effectively clinging to the receptor.
3D Structure Analysis Provides Key Insights
The researchers successfully pinpointed the precise interaction site on both paxillin and integrin, unveiling the previously unknown 3D architecture of this section of paxillin.
“We uncovered a vital piece of the puzzle concerning the interaction between these two proteins by identifying the exact integrin binding site in the context of paxillin’s 3D structure. In paxillin, this segment resembles a movable flap that likely grips integrin like a clamp but can easily be released,” explains chemist Möller. Cell biologist Hauck adds, “Essentially, the flexibility of this portion of paxillin seems to enhance the overall motility of cells by attaching to and releasing from integrin.”
Implications for Medical Applications
Heiko Möller’s research group in Potsdam analyzed these dynamic protein structures using nuclear magnetic resonance spectroscopy (NMR). “This provided a foundation for our team in Konstanz to create specific variants of paxillin and integrins and investigate their effects on the formation and structure of focal adhesions in living cells. We can now formulate new hypotheses about the mechanisms behind their formation and remodeling,” says Hauck.
In the medical field, substances that alter integrins and their adhesion capabilities are currently employed to prevent heart attacks or treat inflammatory bowel diseases. The scientists are optimistic that their findings will lead to the development of new active substances that specifically target cellular adhesion points.
