A two-tier Golgi-based control of organelle size underpins the functional plasticity of endothelial cells.
A two-tier Golgi-based control of organelle size underpins the functional plasticity of endothelial cells.
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基于两层高尔基体的细胞器大小的控制基于内皮细胞的功能可塑性。
DOI：
10.1016/j.devcel.2014.03.021
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发表时间：
2014-05-12
影响因子：
11.8
通讯作者：
Cutler, Daniel F.
中科院分区：
文献类型：
--
作者：
Ferraro, Francesco;Kriston-Vizi, Janos;Metcalf, Daniel J.;Martin-Martin, Belen;Freeman, Jamie;Burden, Jemima J.;Westmoreland, David;Dyer, Clare E.;Knight, Alex E.;Ketteler, Robin;Cutler, Daniel F.
webel - palade小体（WPBs）是内皮特异性分泌颗粒，在原发性止血和炎症中起核心作用，尺寸在0.5 ~ 5 μm之间。它们的大小是如何确定的，以及它是否与功能相关，目前尚不清楚。在这里，我们提供了高尔基体在控制这些分泌载体大小方面的双重作用的证据。在微型层面上，蓄水池限制了von Willebrand因子（vWF）的纳米结构（“量子”）的大小，vWF是WPB的主要载体。高尔基结构的带状结构允许在跨高尔基网络的连续腔内封装可变数量的vWF量子，从而产生不同大小的细胞器。减少WPB的大小会通过显著减少血小板募集来减弱内皮细胞的止血功能，但是，引人注目的是，炎症反应（内皮细胞与白细胞接触的能力）没有改变。因此，大小可以通过对细胞器活动的不同影响而赋予其功能可塑性。高尔基体中的贮池长度控制着vWF载运纳米结构的大小，高尔基带允许将vWF纳米结构共包装到可变大小的WPBs中，小WPBs的内皮细胞显示出血小板募集能力降低，细胞器大小的控制可能赋予内皮止血的可塑性，韦贝尔-帕拉体是内皮介导的止血和炎症起始的分泌颗粒。Ferraro等人表明，高尔基带结构是由vWF货物的水箱模塑量子组装大型wpb所必需的。细胞器大小的变化影响血小板的募集，但不影响白细胞的募集，赋予内皮细胞功能可塑性。
Weibel-Palade bodies (WPBs), endothelial-specific secretory granules that are central to primary hemostasis and inflammation, occur in dimensions ranging between 0.5 and 5 μm. How their size is determined and whether it has a functional relevance are at present unknown. Here, we provide evidence for a dual role of the Golgi apparatus in controlling the size of these secretory carriers. At the ministack level, cisternae constrain the size of nanostructures (“quanta”) of von Willebrand factor (vWF), the main WPB cargo. The ribbon architecture of the Golgi then allows copackaging of a variable number of vWF quanta within the continuous lumen of the trans-Golgi network, thereby generating organelles of different sizes. Reducing the WPB size abates endothelial cell hemostatic function by drastically diminishing platelet recruitment, but, strikingly, the inflammatory response (the endothelial capacity to engage leukocytes) is unaltered. Size can thus confer functional plasticity to an organelle by differentially affecting its activities. Cisternal length within Golgi ministacks controls the size of vWF cargo nanostructures The Golgi ribbon allows copackaging of vWF nanostructures into WPBs of variable size Endothelial cells with small WPBs display a reduced platelet recruitment capability Control of organelle size may confer hemostatic plasticity to endothelia Weibel-Palade bodies are secretory granules central to the initiation of endothelial-mediated hemostasis and inflammation. Ferraro et al. show that Golgi ribbon architecture is required for assembly of large WPBs from cisterna-molded quanta of vWF cargo. Organelle size changes affect recruitment of platelets, but not leukocytes, conferring functional plasticity to endothelia.
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