The Role of Filamin A in Blood Clotting: How Platelets Change Shape to Stop Bleeding

December 4, 2024

Written by: Rhonda Thygesen, CBR Alumni

Edited by: Alexandra Witt, PhD Candidate, Pryzdial Lab

Figure 1: How FLNA helps control cell contraction in platelets.

Figure 1: How FLNA helps control cell contraction in platelets.

Blood clotting is essential to stop bleeding after an injury. When blood vessels are damaged, tiny cells in the blood called platelets rush to the site and change shape to work together and form a clot. This shape-changing ability is critical for platelets to effectively plug the injury and prevent excessive bleeding.

The Kim lab in the CBR has been studying how platelets make these changes, specifically focusing on a protein called Filamin A (FLNA), which plays a crucial role in the shape-shifting process1. FLNA is a protein that binds to actin, a component of the cell’s skeleton. In platelets, FLNA helps to stabilize this skeleton, acting like a scaffold to hold together the parts of the cell that are necessary for changing shape and generating the force required to form a clot2.

Researchers in the Kim lab conducted an experiment using platelets from mice with a platelet-specific deletion of FLNA1. They found that platelets without FLNA couldn’t generate the force required to create a stable clot, with decreased contractile abilities making their clots weaker and far less retracted.

During clot maturation, platelets retract to reduce clot volume and draw the edges of the wound together. Looking into the role FLNA was playing, they investigated its interactions with other proteins that control cell contraction, such as Rho-kinase (ROCK) and protein kinase C (PKC)3. These proteins help activate myosin, a protein that works alongside actin to generate force. Without FLNA to act as a scaffolding protein for actin, the activity of these proteins was reduced, failing to allow for phosphorylation of myosin light chain (MLC) phosphatase and ultimately, clot retraction (Figure 1).

Understanding the role of FLNA in blood clotting helps us get a clearer picture of how platelets function and what can go wrong in clotting disorders. By uncovering the role of FLNA, scientists are gaining insights that may lead to better treatments for blood clotting issues, potentially helping people who struggle with excessive bleeding.

Figure 1: How FLNA helps control cell contraction in platelets. This diagram shows how the protein FLNA plays a role in cell shape changes by regulating the contraction of actin and myosin, key parts of the cell’s structural framework. (A) When thrombin, a blood-clotting protein, activates the platelet, FLNA helps other proteins (RhoA and ROCK) inhibit a process that would normally stop contraction, leading to successful clot retraction. (B) FLNA also works with another protein, PKC, to promote the same process. Together, these mechanisms help platelets change shape and play their role in blood clotting.

References

  1. Hong, F., Mollica, M. Y., Golla, K., De Silva, E., Sniadecki, N. J., López, J. A., & Kim, H. (2024). Filamin A regulates platelet shape change and contractile force generation via phosphorylation of the myosin light chain. Biochemical Journal, 481(20), 1395-1410.
  2. Rosa, J. P., Raslova, H., & Bryckaert, M. (2019). Filamin A: key actor in platelet biology. Blood, the Journal of the American Society of Hematology, 134(16), 1279-1288.
  3. Hong, F. (2023). The role of filamin A in modulating platelet shape change(Doctoral dissertation, UNIVERSITY OF BRITISH COLUMBIA (Vancouver).