Image by Andre E.X. Brown
Preclinical research has unearthed additional information about how platelets respond to shear stress, answering a 20-year-old question.
Investigators said this research provides new insights regarding platelet activation and clearance as well as insights into the pathophysiology of von Willebrand disease and related thrombocytopenic disorders.
The team described this work in Nature Communications.
Past research suggested that platelets respond to shear stress through a protein complex called GPIb-IX located on the platelet surface, but how this complex senses and responds to shear stress has remained a mystery for the past 20 years.
With the current study, investigators found that, contrary to popular belief, a certain region within GPIb-IX is structured.
This so-called mechanosensory domain (MSD) becomes unfolded on the platelet surface when von Willebrand factor binds to the GPIbα subunit of GPIb–IX under shear stress and imposes a pulling force on it.
The unfolding of MSD sets off a complex chain of events and sends an intracellular signal into the platelet that results in rapid platelet clearance.
“Every day, your bone marrow generates more than a billion platelets, and, every day, you clear the same number,” said study author Renhao Li, PhD, of Emory University School of Medicine in Atlanta, Georgia.
“It’s critical that your platelet count stays constant. Too few platelets can lead to . . . thrombocytopenia and may cause spontaneous bleeding or stroke. Thus, identifying the molecular ‘switch’ that triggers platelet clearance is important for designing new therapies to treat thrombocytopenia.”
The mechanism behind MSD-unfolding-induced platelet clearance is still unclear, but Dr Li said this research provides a good starting point for further inquiry into the phenomenon.
