Weibel-Palade bodies recruit Rab27 by a content-driven, maturation-dependent mechanism that is independent of cell type
Weibel-Palade bodies recruit Rab27 by a content-driven, maturation-dependent mechanism that is independent of cell type
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DOI：
10.1242/jcs.00711
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发表时间：
2003-10-01
影响因子：
4
通讯作者：
Cutler, DF
中科院分区：
文献类型：
--
作者：
Hannah, MJ;Hume, AN;Cutler, DF
细胞器的识别对于有效的细胞功能至关重要，但可能发生这种情况的基本机制尚未建立。一组可能对细胞器身份至关重要的蛋白质是小GTP酶的Rab家族。因此，我们研究了Rab招聘膜使用内皮细胞作为模型系统。我们报告说，韦伯-帕拉德机构，人脐静脉内皮细胞的血管性血友病因子的存储隔间，包含Rab 27 a。我们还发现，在HEK-293细胞中通过表达von Willebrand因子诱导的韦伯-帕拉德体样结构可以募集内源性Rab 27 a。在缺乏von Willebrand因子的情况下，Rab 27 a不与溶酶体相关，表明它可以区分韦伯-帕拉德体样细胞器和经典溶酶体。最后，使用绿色荧光版本的冯维勒布兰德因子建立了韦伯-帕拉德体形成的时间过程。新形成的韦伯-帕拉德体缺乏Rab 27 a，这是在雪茄状细胞器最初出现后几小时获得的。我们的结论是，内腔货物蛋白驱动招聘Rab 27 a的细胞器膜的一种新的机制，是间接的，成熟依赖性和细胞类型的独立。
The identification of organelles is crucial for efficient cellular function, yet the basic underlying mechanisms by which this might occur have not been established. One group of proteins likely to be central to organelle identity is the Rab family of small GTPases. We have thus investigated Rab recruitment to membranes using endothelial cells as a model system. We report that Weibel-Palade bodies, the Von Willebrand Factor storage compartment of human umbilical vein endothelial cells, contain Rab27a. We have also found that Weibel-Palade body-like structures induced in HEK-293 cells by the expression of von Willebrand factor can recruit endogenous Rab27a. In the absence of von Willebrand Factor, Rab27a is not lysosome associated, indicating that it can distinguish between the Weibel-Palade-body-like organelle and a classical lysosome. Finally, a time course of Weibel-Palade-body formation was established using a green-fluorescent version of von Willebrand factor. Newly formed Weibel-Palade bodies lack Rab27a, which is acquired some hours after initial appearance of the cigar-shaped organelle. We conclude that a lumenal cargo protein drives the recruitment of Rab27a to the organelle membrane by a novel mechanism that is indirect, maturation-dependent and cell-type independent.