Deletion of the Arp2/3 complex in megakaryocytes leads to microthrombocytopenia in mice

Blood Advances
David S PaulWolfgang Bergmeier

Abstract

Actin reorganization regulates key processes in platelet activation. Here we examined the role of the Arp2/3 complex, an essential component in actin filament branching, in platelet function. The Arpc2 gene, encoding the p34 subunit of the Arp2/3 complex, was deleted in the megakaryocyte lineage (Arpc2fl/flPF4-Cre). Deletion of the Arp2/3 complex resulted in marked microthrombocytopenia in mice, caused by premature platelet release into the bone marrow compartment and impaired platelet survival in circulation. Arpc2fl/flPF4-Cre platelets exhibited alterations in their actin cytoskeleton and their peripheral microtubule coil. Thrombocytopenia was alleviated following clodronate liposome-induced macrophage depletion in Arpc2fl/flPF4-Cre mice. Arpc2fl/flPF4-Cre platelets failed to spread and showed a mild defect in integrin activation and aggregation. However, no significant differences in hemostasis or thrombosis were observed between Arpc2fl/flPF4-Cre and control mice. Thus, Arp2/3 is critical for platelet homeostasis but plays only a minor role for vascular hemostasis.

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Citations

Jun 19, 2018·Platelets·Irina PleinesMarkus Bender
Jul 10, 2018·Current Opinion in Hematology·Harvey G RowethKellie R Machlus
Jun 21, 2019·Journal of Thrombosis and Haemostasis : JTH·Dorsaf GhalloussiWolfgang Bergmeier
Nov 12, 2019·The Journal of Clinical Investigation·Lyra O RandzavolaGillian M Griffiths
May 26, 2018·Platelets·Joseph E Aslan
Jan 14, 2020·Journal of Thrombosis and Haemostasis : JTH·Hannah L H GreenSteven G Thomas
Jan 29, 2020·Research and Practice in Thrombosis and Haemostasis·Yosuke MorodomiTaisuke Kanaji
Sep 29, 2020·Platelets·Malou ZuidscherwoudeSteven G Thomas
Feb 12, 2021·Small GTPases·William VainchenkerHana Raslova
Feb 16, 2021·Hämostaseologie·Markus Bender, Raghavendra Palankar
Nov 15, 2020·Nature Communications·Leo NicolaiFlorian Gaertner

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