Role of Alpha Granule Secretion in Platelet Glucose Metabolism

Platelets play a critical role in hemostasis and thrombosis through their activation, shape change, secretion, and aggregation. These highly metabolically active cells shift from a low-energy resting state to a high-energy activated state. Platelet secretion is a key step in hemostasis, involving the release of cargo from alpha, dense, and lysosomal granules, which merge with the plasma membrane to modify the local environment to help form a clot achieving hemostasis.

Alpha granules, the most numerous and diverse, are crucial for platelet functions such as hemostasis, inflammation, immunity, wound healing, and angiogenesis. They contain numerous bioactive proteins, including integrins, immunoglobulin family receptors, and GLUT3, a glucose transporter.

In resting conditions, GLUT3 is found in alpha granules but translocates to the plasma membrane upon platelet activation, facilitating glucose uptake necessary for platelet function. GLUT3 deletion impairs platelet activation and function, highlighting the importance of glucose metabolism.

This study, using the V2Δ3Δ8-/- mouse model with deficient SNARE proteins, reveals that GLUT3 translocation is critical for platelet secretion and clot formation. We show clot contraction defect in V2Δ3Δ8-/- platelets that can be rescued by the addition of pyruvate (downstream intermediate metabolite whose destiny is determined by the availability of oxygen within the environment) indicating the metabolic aspect of platelet secretion. Further research is needed to understand GLUT3 levels in these mice. Our findings underscore the link between platelet secretion and metabolism, showing that GLUT3 translocation from granules to the surface is crucial for platelet function and metabolism.

No relevant conflicts of interest to declare.