Identification of a vesicular nucleotide transporter
Identification of a vesicular nucleotide transporter
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DOI：
10.1073/pnas.0800141105
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发表时间：
2008-04-15
影响因子：
11.1
通讯作者：
Moriyama, Yoshinori
中科院分区：
文献类型：
--
作者：
Sawada, Keisuke;Echigo, Noriko;Moriyama, Yoshinori
ATP是嘌呤能信号传递的主要化学递质。在分泌前，ATIP储存在嘌呤能细胞中发现的分泌囊泡中。虽然ATP的主动转运机制的存在已经被假定了很长一段时间，负责其囊泡积累的蛋白质仍然未知。人和小鼠SLC17A9基因编码的转运蛋白是阴离子转运蛋白家族的新成员，主要在脑和肾上腺中表达。小鼠和牛对应物与肾上腺嗜铬颗粒相关。含有纯化转运蛋白的蛋白脂质体以膜电位为驱动力，主动摄取ATP、ADP和GTP。重组转运蛋白的摄取特性与突触囊泡和嗜铬颗粒的ATP摄取特性相似。抑制内源性SLC 17A9在PC12细胞中的表达减少ATP的胞吐。这些研究结果强烈表明，SLC17A9蛋白是一种囊泡核苷酸转运蛋白，并应导致嘌呤信号传递的ATP分泌的分子机制的阐明。
ATP is a major chemical transmitter in purinergic signal transmission. Before secretion, ATIP is stored in secretory vesicles found in purinergic cells. Although the presence of active transport mechanisms for ATP has been postulated for a long time, the proteins responsible for its vesicular accumulation remains unknown. The transporter encoded by the human and mouse SLC17A9 gene, a novel member of an anion transporter family, was predominantly expressed in the brain and adrenal gland. The mouse and bovine counterparts were associated with adrenal chromaffin granules. Proteoliposomes containing purified transporter actively took up ATP, ADP, and GTP by using membrane potential as the driving force. The uptake properties of the reconstituted transporter were similar to that of the ATP uptake by synaptic vesicles and chromaffin granules. Suppression of endogenous SLC17A9 expression in PC12 cells decreased exocytosis of ATP. These findings strongly suggest that SLC17A9 protein is a vesicular nucleotide transporter and should lead to the elucidation of the molecular mechanism of ATP secretion in purinergic signal transmission.