Coactosin-like 1 integrates signaling critical for shear-dependent thrombus formation in mouse platelets.

Coactosin-like 1 integrates signaling critical for shear-dependent thrombus formation in mouse platelets. Haematologica. 2019 Oct 03;: Authors: Scheller I, Stritt S, Beck S, Peng B, Pleines I, Heinze KG, Braun A, Otto O, Ahrends R, Sickmann A, Bender M, Nieswandt B Abstract Platelet aggregate formation is a multistep process involving receptor-mediated, as well as biomechanical signaling cascades, which are highly dependent on actin dynamics. We have previously shown that actin depolymerizing factor (ADF)/n-cofilin and Twinfilin 2a, members of the ADF homology (ADF-H) protein family, have distinct roles in platelet formation and function. Coactosin-like 1 (Cotl1) is another ADF-H protein that binds actin and was additionally shown to enhance biosynthesis of pro-inflammatory leukotrienes (LTs) in granulocytes. Here, we generated mice lacking Cotl1 in the megakaryocyte lineage (Cotl1-/-) to investigate its role in platelet production and function. Absence of Cotl1 had no impact on platelet counts, platelet activation and cytoskeletal reorganization under static conditions in vitro. In contrast, Cotl1 deficiency markedly affected platelet aggregate formation on collagen and adhesion to immobilized von Willebrand factor (vWF) at high shear rates in vitro, pointing to an impaired function of the platelet mechanoreceptor glycoprotein (GP) Ib. Cotl1-/- platelets furthermore exhibited increased deformability at high shear rates, indicating t...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research