Rudolf Virchow Center, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
Blood. 2010 Sep 9;116(10):1767-75. doi: 10.1182/blood-2010-03-274340. Epub 2010 Jun 7.
The cellular and molecular mechanisms orchestrating the complex process by which bone marrow megakaryocytes form and release platelets remain poorly understood. Mature megakaryocytes generate long cytoplasmic extensions, proplatelets, which have the capacity to generate platelets. Although microtubules are the main structural component of proplatelets and microtubule sliding is known to drive proplatelet elongation, the role of actin dynamics in the process of platelet formation has remained elusive. Here, we tailored a mouse model lacking all ADF/n-cofilin-mediated actin dynamics in megakaryocytes to specifically elucidate the role of actin filament turnover in platelet formation. We demonstrate, for the first time, that in vivo actin filament turnover plays a critical role in the late stages of platelet formation from megakaryocytes and the proper sizing of platelets in the periphery. Our results provide the genetic proof that platelet production from megakaryocytes strictly requires dynamic changes in the actin cytoskeleton.
骨髓巨核细胞形成和释放血小板的复杂过程的细胞和分子机制仍知之甚少。成熟的巨核细胞会产生长的细胞质延伸，即前血小板，它具有生成血小板的能力。虽然微管是前血小板的主要结构成分，并且已知微管滑动可驱动前血小板伸长，但在血小板形成过程中肌动蛋白动力学的作用仍然难以捉摸。在这里，我们构建了一种缺乏巨核细胞中所有 ADF/n-cofilin 介导的肌动蛋白动力学的小鼠模型，专门阐明肌动蛋白丝周转率在血小板形成中的作用。我们首次证明，在体内，肌动蛋白丝周转率在巨核细胞向血小板形成的晚期以及外周血小板的适当大小中起着关键作用。我们的研究结果提供了遗传证据，证明巨核细胞产生血小板严格需要肌动蛋白细胞骨架的动态变化。
