Essential role of vesicular nucleotide transporter in vesicular storage and release of nucleotides in platelets.

Essential role of vesicular nucleotide transporter in vesicular storage and release of nucleotides in platelets.
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DOI:
10.14814/phy2.12034
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发表时间:
2014-06-01
影响因子:
2.5
通讯作者:
Moriyama Y
Moriyama Y
中科院分区:
其他
文献类型:
--
作者:
Hiasa M;Togawa N;Miyaji T;Omote H;Yamamoto A;Moriyama Y

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核苷酸储存在血小板的致密颗粒中。核苷酸的释放触发了一系列导致血液凝固的级联反应的第一步。然而,核苷酸如何在颗粒中积累的机制仍然知之甚少。在神经内分泌细胞中负责核苷酸储存的转运蛋白已经被鉴定和表征。我们假设囊泡核苷酸转运蛋白(VNUT)也参与了血小板中核苷酸的囊泡储存。在本文中,我们提出了三条证据,证明VNUT负责血小板中核苷酸的囊泡储存,而囊泡ATP转运对于血小板功能、健康人和MEG‐01细胞分离的血小板中VNUT活性的检测和表征、MEG‐01细胞的RNA干扰实验以及选择性抑制剂对核苷酸转运和释放的研究至关重要。VNUT在血小板中高度表达并与致密颗粒相关。VNUT在血小板中核苷酸的囊泡储存中起重要作用。
Nucleotides are stored in the dense granules of platelets. The release of nucleotides triggers one of the first steps in a series of cascades responsible for blood coagulation. However, the mechanism of how the nucleotides are accumulated in the granules is still far less understood. The transporter protein responsible for storage of nucleotides in the neuroendocrine cells has been identified and characterized. We hypothesized that the vesicular nucleotide transporter (VNUT) is also involved in the vesicular storage of nucleotides in platelets. In this article, we present three lines of evidence that VNUT is responsible for the vesicular storage of nucleotides in platelets and that vesicular ATP transport is crucial for platelet function, detection and characterization of VNUT activity in platelets isolated from healthy humans and MEG‐01 cells, RNA interference experiments on MEG‐01 cells, and studies on nucleotide transport and release with a selective inhibitor. VNUT is highly expressed and associated with dense granules in platelets. VNUT plays an essential role in vesicular storage of nucleotide in platelets.