Na(+) dependent acid-base transporters in the choroid plexus; insights from slc4 and slc9 gene deletion studies.
Na(+) dependent acid-base transporters in the choroid plexus; insights from slc4 and slc9 gene deletion studies.
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DOI：
10.3389/fphys.2013.00304
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发表时间：
2013-10-22
影响因子：
4
通讯作者：
Damkier HH
中科院分区：
文献类型：
--
作者：
Christensen HL;Nguyen AT;Pedersen FD;Damkier HH
脉络丛上皮（CPE）位于脑的脑室系统中，在那里它分泌填充脑室系统并包围中枢神经系统的大部分脑脊液（CSF）。CPE是高度血管化的单层立方细胞，具有无与伦比的跨上皮水和溶质转运速率。碳酸氢盐转运蛋白的slc 4a家族的几个成员在CPE中表达。在基底外侧膜中，表达电中性Na+依赖性Cl−/HCO 3 −交换器，NCBE（slc 4a 10）。在腔膜中，表达产电Na+：HCO 3 −协同转运蛋白NBCe 2（slc 4a 5）。电子中性Na+：HCO 3 −协同转运蛋白NBCn 1（slc 4a 7）位于两种膜上。除了碳酸氢盐转运蛋白外，Na+/H+交换剂NHE 1（slc 9a 1）位于CPE的腔膜中。已经产生了靶向slc 4a 2、slc 4a 5、slc 4a 7、slc 4a 10和slc 9a 1的遗传修饰小鼠。slc 4a 5、7或10或slc 9a 1的缺失对这些小鼠中的CP功能和结构具有许多影响。转运蛋白的去除影响脑室大小（slc 4a 5和slc 4a 10）和细胞内pH调节（slc 4a 7和slc 4a 10）。在一些情况下，从CPE（slc 4a 5、7和10）去除蛋白质引起已知参与pH调节和CSF分泌的非靶转运蛋白的丰度和定位的变化。本综述的重点是联合收割机收集的见解，从这些敲除小鼠突出的影响，slc 4基因缺失的CSF生产和细胞内的pH调节所造成的slc 4a 5，7和10，slc 9a 1的删除。此外，该综述还将这些基因的人类突变与敲除研究中的发现进行了比较。最后，将讨论利用这些蛋白质作为治疗CSF疾病的潜在靶点的未来前景。
The choroid plexus epithelium (CPE) is located in the ventricular system of the brain, where it secretes the majority of the cerebrospinal fluid (CSF) that fills the ventricular system and surrounds the central nervous system. The CPE is a highly vascularized single layer of cuboidal cells with an unsurpassed transepithelial water and solute transport rate. Several members of the slc4a family of bicarbonate transporters are expressed in the CPE. In the basolateral membrane the electroneutral Na+ dependent Cl−/HCO3− exchanger, NCBE (slc4a10) is expressed. In the luminal membrane, the electrogenic Na+:HCO3− cotransporter, NBCe2 (slc4a5) is expressed. The electroneutral Na+:HCO3− cotransporter, NBCn1 (slc4a7), has been located in both membranes. In addition to the bicarbonate transporters, the Na+/H+ exchanger, NHE1 (slc9a1), is located in the luminal membrane of the CPE. Genetically modified mice targeting slc4a2, slc4a5, slc4a7, slc4a10, and slc9a1 have been generated. Deletion of slc4a5, 7 or 10, or slc9a1 has numerous impacts on CP function and structure in these mice. Removal of the transporters affects brain ventricle size (slc4a5 and slc4a10) and intracellular pH regulation (slc4a7 and slc4a10). In some instances, removal of the proteins from the CPE (slc4a5, 7, and 10) causes changes in abundance and localization of non-target transporters known to be involved in pH regulation and CSF secretion. The focus of this review is to combine the insights gathered from these knockout mice to highlight the impact of slc4 gene deletion on the CSF production and intracellular pH regulation resulting from the deletion of slc4a5, 7 and 10, and slc9a1. Furthermore, the review contains a comparison of the described human mutations of these genes to the findings in the knockout studies. Finally, the future perspective of utilizing these proteins as potential targets for the treatment of CSF disorders will be discussed.
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DOI：
10.1152/ajpcell.1999.276.4.c788
发表时间：
1999-04-01
影响因子：
5.5
作者：
Bell, SM;Schreiner, CM;Scott, WJ
通讯作者：
Scott, WJ
影响因子：
5.5
作者：
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通讯作者：
Praetorius, Jeppe
影响因子：
64.8
作者：
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通讯作者：
Boron, WF
影响因子：
5.5
作者：
Chen, Mingmin;Praetorius, Jeppe;Seidler, Ursula
通讯作者：
Seidler, Ursula
影响因子：
37.8
作者：
Boedtkjer, Ebbe;Praetorius, Jeppe;Aalkjaer, Christian
通讯作者：
Aalkjaer, Christian