Identification of a mammalian vesicular polyamine transporter.

Identification of a mammalian vesicular polyamine transporter.
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DOI:
10.1038/srep06836
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发表时间:
2014-10-30
期刊:
影响因子:
4.6
通讯作者:
Moriyama Y
Moriyama Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hiasa M;Miyaji T;Haruna Y;Takeuchi T;Harada Y;Moriyama S;Yamamoto A;Omote H;Moriyama Y

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精胺和亚精胺在与N-甲基-d-天冬氨酸受体等多种亲离子受体的胞外部位(S)结合时,起到神经调节剂的作用。为了获得受体,神经元和星形胶质细胞合成的多胺被储存在分泌小泡中,并在去极化时释放。尽管囊泡储存是以ATP依赖的、利血平敏感的方式调节的,但负责这一过程的转运体仍然未知。SLC18B1是SLC18转运体家族的第四个成员,包括囊泡单胺转运体和囊泡乙酰胆碱转运体。含有纯化的人SLC18B1蛋白的蛋白质脂质体通过H+交换来转运精胺和亚精胺。SLC18B1蛋白主要在海马区表达,与星形胶质细胞中的囊泡有关。SLC18B1基因敲除后,星形胶质细胞中SLC18B1蛋白和精胺/亚精胺含量均降低。这些结果表明SLC18B1编码一种囊泡性多胺转运蛋白(VPAT)。
Spermine and spermidine act as neuromodulators upon binding to the extracellular site(s) of various ionotropic receptors, such as N-methyl-d-aspartate receptors. To gain access to the receptors, polyamines synthesized in neurons and astrocytes are stored in secretory vesicles and released upon depolarization. Although vesicular storage is mediated in an ATP-dependent, reserpine-sensitive fashion, the transporter responsible for this process remains unknown. SLC18B1 is the fourth member of the SLC18 transporter family, which includes vesicular monoamine transporters and vesicular acetylcholine transporter. Proteoliposomes containing purified human SLC18B1 protein actively transport spermine and spermidine by exchange of H+. SLC18B1 protein is predominantly expressed in the hippocampus and is associated with vesicles in astrocytes. SLC18B1 gene knockdown decreased both SLC18B1 protein and spermine/spermidine contents in astrocytes. These results indicated that SLC18B1 encodes a vesicular polyamine transporter (VPAT).
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