The vesicular amine transporter family (SLC18):: amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine

The vesicular amine transporter family (SLC18):: amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine
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DOI:
10.1007/s00424-003-1100-5
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发表时间:
2004-02-01
影响因子:
4.5
通讯作者:
Schütz, B
Schütz, B
中科院分区:
医学3区
文献类型:
--
作者:
Eiden, LE;Schäfer, MKH;Schütz, B

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囊泡胺转运蛋白(VATs)是神经细胞和内分泌细胞分泌囊泡脂双层膜的组成蛋白。它们的功能是允许乙酰胆碱(通过囊泡乙酰胆碱转运蛋白VAChT; SLC 18 A3)和生物胺(通过囊泡单胺转运蛋白VMAT 1和VMAT 2; SLC 18 A1和SLC 18 A2)转运到分泌囊泡中,然后通过胞吐作用将它们排放到细胞外空间。在所有情况下,SLC 18家族成员转运带正电荷的胺都是利用通过液泡ATP酶将质子泵入囊泡而建立的跨囊泡膜的电化学梯度;胺以质子梯度为代价在囊泡中积累,比例为每两个易位的质子一个易位的胺。SLC 18家族成员已成为神经内分泌组织和细胞中化学编码的重要组织化学标记。他们的显着能力,运输带正电荷的胺对一个非常大的浓度梯度,以及潜在的疾病与受损的转运蛋白功能和表达的结构基础,正在紧张的调查。
The vesicular amine transporters (VATs) are expressed as integral proteins of the lipid bilayer membrane of secretory vesicles in neuronal and endocrine cells. Their function is to allow the transport of acetylcholine (by the vesicular acetylcholine transporter VAChT; SLC18A3) and biogenic amines (by the vesicular monoamine transporters VMAT1 and VMAT2; SLC18A1 and SLC18A2) into secretory vesicles, which then discharge them into the extracellular space by exocytosis. Transport of positively charged amines by members of the SLC18 family in all cases utilizes an electrochemical gradient across the vesicular membrane established by proton pumping into the vesicle via a vacuolar ATPase; the amine is accumulated in the vesicle at the expense of the proton gradient, at a ratio of one translocated amine per two translocated protons. The members of the SLC18 family have become important histochemical markers for chemical coding in neuroendocrine tissues and cells. The structural basis of their remarkable ability to transport positively charged amines against a very large concentration gradient, as well as potential disease association with impaired transporter function and expression, are under intense investigation.