a Institute of Experimental Biomedicine I , University Hospital and Rudolf Virchow Center, University of Würzburg , Würzburg , Germany.
b Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Pediatrics , Harvard Medical School , Boston , MA , USA.
Platelets. 2019;30(1):9-16. doi: 10.1080/09537104.2018.1478071. Epub 2018 Jun 18.
Megakaryocytes differentiate from hematopoietic stem cells in the bone marrow. The transition of megakaryocytes to platelets is a complex process. Thereby, megakaryocytes extend proplatelets into sinusoidal blood vessels, where the proplatelets undergo fission to release platelets. Defects in platelet production can lead to a low platelet count (thrombocytopenia) with increased bleeding risk. Rho GTPases comprise a family of small signaling G proteins that have been shown to be master regulators of the cytoskeleton controlling many aspects of intracellular processes. The generation of Pf4-Cre transgenic mice was a major breakthrough that enabled studies in megakaryocyte-/platelet-specific knockout mouse lines and provided new insights into the central regulatory role of Rho GTPases in megakaryocyte maturation and platelet production. In this review, we will summarize major findings on the role of Rho GTPases in megakaryocyte biology with a focus on mouse lines in which knockout strategies have been applied to study the function of the best-characterized members Rac1, Cdc42 and RhoA and their downstream effector proteins.
巨核细胞从骨髓中的造血干细胞中分化而来。巨核细胞向血小板的转化是一个复杂的过程。因此，巨核细胞将前血小板延伸到窦状血管中，在前血小板中发生裂变以释放血小板。血小板生成缺陷可导致血小板计数降低（血小板减少症），出血风险增加。Rho GTPases 是一个小信号 G 蛋白家族，已被证明是细胞骨架的主要调节剂，控制着许多细胞内过程的方面。Pf4-Cre 转基因小鼠的产生是一项重大突破，使巨核细胞/血小板特异性敲除小鼠系的研究成为可能，并为 Rho GTPases 在巨核细胞成熟和血小板生成中的中心调节作用提供了新的见解。在这篇综述中，我们将总结 Rho GTPases 在巨核细胞生物学中的主要作用，重点介绍已应用于研究研究最具特征性的 Rac1、Cdc42 和 RhoA 及其下游效应蛋白功能的敲除策略的小鼠系。
