The spectrin-based membrane skeleton stabilizes mouse megakaryocyte membrane systems and is essential for proplatelet and platelet formation
The spectrin-based membrane skeleton stabilizes mouse megakaryocyte membrane systems and is essential for proplatelet and platelet formation
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DOI：
10.1182/blood-2011-01-330688
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发表时间：
2011-08-11
期刊：
影响因子：
20.3
通讯作者：
Italiano, Joseph E., Jr.
中科院分区：
文献类型：
--
作者：
Patel-Hett, Sunita;Wang, Hongbei;Italiano, Joseph E., Jr.
巨核细胞通过将其细胞质首先重塑为前血小板，然后重塑为前血小板来产生血小板，前血小板经过裂变产生血小板。尽管微管和肌动蛋白在血小板生物发生过程中的功能已被确定，但血影蛋白细胞骨架的作用尚不清楚。我们研究了基于血影蛋白的膜骨架在鼠巨核细胞中前血小板和血小板生成中的功能。电子显微镜显示，与循环血小板一样，前血小板具有致密的膜骨架，其主要纤维成分是血影蛋白。与其他细胞不同，巨核细胞及其后代表达红系血影蛋白和非红系血影蛋白。内陷膜系统成熟和前血小板延伸需要将血影蛋白组装成四聚体，因为巨核细胞中血影蛋白四聚体破坏构建体的表达会抑制这两个过程。将这种血影蛋白破坏片段掺入新型透化前血小板系统中，会迅速破坏前血小板的稳定性，导致起泡和肿胀。血影蛋白四聚体还可以稳定血小板生成过程中倒数第二阶段的“杠铃形状”，因为添加四聚体破坏结构会将这些杠铃形状转化为球体，这表明膜骨架连续性保持了细长的裂变前形状。这项研究的结果为血影蛋白通过参与内陷膜的形成和前血小板结构的维持在巨核细胞发育的不同步骤中的作用提供了证据。 （血。2011；118（6）：1641-1652）
Megakaryocytes generate platelets by remodeling their cytoplasm first into proplatelets and then into preplatelets, which undergo fission to generate platelets. Although the functions of microtubules and actin during platelet biogenesis have been defined, the role of the spectrin cytoskeleton is unknown. We investigated the function of the spectrin-based membrane skeleton in proplatelet and platelet production in murine megakaryocytes. Electron microscopy revealed that, like circulating platelets, proplatelets have a dense membrane skeleton, the main fibrous component of which is spectrin. Unlike other cells, megakaryocytes and their progeny express both erythroid and nonerythroid spectrins. Assembly of spectrin into tetramers is required for invaginated membrane system maturation and proplatelet extension, because expression of a spectrin tetramer-disrupting construct in megakaryocytes inhibits both processes. Incorporation of this spectrin-disrupting fragment into a novel permeabilized proplatelet system rapidly destabilizes proplatelets, causing blebbing and swelling. Spectrin tetramers also stabilize the "barbell shapes" of the penultimate stage in platelet production, because addition of the tetramer-disrupting construct converts these barbell shapes to spheres, demonstrating that membrane skeletal continuity maintains the elongated, pre-fission shape. The results of this study provide evidence for a role for spectrin in different steps of megakaryocyte development through its participation in the formation of invaginated membranes and in the maintenance of proplatelet structure. (Blood. 2011;118(6): 1641-1652)