Gray platelet syndrome (GPS; aka platelet alpha-granule deficiency) is a rare congenital bleeding disorder that is caused by mutations in the gene NBEAL2. Using transgenic Nbeal2-deficient mice, Carsten Depperman and colleagues characterized the pathological mechanisms that underlie GPS. Nbeal2-deficiency caused defective alpha-granule biogenesis in megakaryocytes (the cellular precursors of platelets) and impaired platelet adhesion, aggregation, and coagulant activity in models of thrombo-inflammatory disease and tissue repair. These findings demonstrate that alpha-granules are required for hemostasis and thrombosis during inflammation and wound repair. The accompanying confocal microscopy image shows a megakaryocyte spread on a fibrinogen matrix and stained for actin (red) and alpha-tubulin (green). Nuclei are highlighted with DAPI (blue).
Platelets are anuclear organelle-rich cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity. The major platelet organelles, α-granules, release proteins that participate in thrombus formation and hemostasis. Proteins stored in α-granules are also thought to play a role in inflammation and wound healing, but their functional significance in vivo is unknown. Mutations in NBEAL2 have been linked to gray platelet syndrome (GPS), a rare bleeding disorder characterized by macrothrombocytopenia, with platelets lacking α-granules. Here we show that
Carsten Deppermann, Deya Cherpokova, Paquita Nurden, Jan-Niklas Schulz, Ina Thielmann, Peter Kraft, Timo Vögtle, Christoph Kleinschnitz, Sebastian Dütting, Georg Krohne, Sabine A. Eming, Alan T. Nurden, Beate Eckes, Guido Stoll, David Stegner, Bernhard Nieswandt