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钠/钙交换体:三个哺乳动物基因家族控制钙转运。

Na+/Ca2+ exchangers: three mammalian gene families control Ca2+ transport.

作者信息

Lytton Jonathan

机构信息

Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada T2N 4N1.

出版信息

Biochem J. 2007 Sep 15;406(3):365-82. doi: 10.1042/BJ20070619.

Abstract

Mammalian Na+/Ca2+ exchangers are members of three branches of a much larger family of transport proteins [the CaCA (Ca2+/cation antiporter) superfamily] whose main role is to provide control of Ca2+ flux across the plasma membranes or intracellular compartments. Since cytosolic levels of Ca2+ are much lower than those found extracellularly or in sequestered stores, the major function of Na+/Ca2+ exchangers is to extrude Ca2+ from the cytoplasm. The exchangers are, however, fully reversible and thus, under special conditions of subcellular localization and compartmentalized ion gradients, Na+/Ca2+ exchangers may allow Ca2+ entry and may play more specialized roles in Ca2+ movement between compartments. The NCX (Na+/Ca2+ exchanger) [SLC (solute carrier) 8] branch of Na+/Ca2+ exchangers comprises three members: NCX1 has been most extensively studied, and is broadly expressed with particular abundance in heart, brain and kidney, NCX2 is expressed in brain, and NCX3 is expressed in brain and skeletal muscle. The NCX proteins subserve a variety of roles, depending upon the site of expression. These include cardiac excitation-contraction coupling, neuronal signalling and Ca2+ reabsorption in the kidney. The NCKX (Na2+/Ca2+-K+ exchanger) (SLC24) branch of Na+/Ca2+ exchangers transport K+ and Ca2+ in exchange for Na+, and comprises five members: NCKX1 is expressed in retinal rod photoreceptors, NCKX2 is expressed in cone photoreceptors and in neurons throughout the brain, NCKX3 and NCKX4 are abundant in brain, but have a broader tissue distribution, and NCKX5 is expressed in skin, retinal epithelium and brain. The NCKX proteins probably play a particularly prominent role in regulating Ca2+ flux in environments which experience wide and frequent fluctuations in Na+ concentration. Until recently, the range of functions that NCKX proteins play was generally underappreciated. This situation is now changing rapidly as evidence emerges for roles including photoreceptor adaptation, synaptic plasticity and skin pigmentation. The CCX (Ca2+/cation exchanger) branch has only one mammalian member, NCKX6 or NCLX (Na+/Ca2+-Li+ exchanger), whose physiological function remains unclear, despite a broad pattern of expression.

摘要

哺乳动物的钠钙交换体是一个更大的转运蛋白家族(CaCA(钙/阳离子反向转运体)超家族)三个分支的成员,其主要作用是控制钙离子穿过质膜或细胞内区室的通量。由于胞质溶胶中的钙离子水平远低于细胞外或隔离储存库中的水平,钠钙交换体的主要功能是将钙离子从细胞质中挤出。然而,这些交换体是完全可逆的,因此,在亚细胞定位和分隔离子梯度的特殊条件下,钠钙交换体可能允许钙离子进入,并可能在不同区室之间的钙离子移动中发挥更特殊的作用。钠钙交换体的NCX(钠/钙交换体)[SLC(溶质载体)8]分支包括三个成员:NCX1研究最为广泛,在心脏、大脑和肾脏中广泛表达且含量特别丰富,NCX2在大脑中表达,NCX3在大脑和骨骼肌中表达。NCX蛋白根据表达位点发挥多种作用。这些作用包括心脏兴奋-收缩偶联、神经元信号传导和肾脏中的钙离子重吸收。钠钙交换体的NCKX(钠2+/钙2+-钾+交换体)(SLC24)分支以钠交换钾和钙,包括五个成员:NCKX1在视网膜视杆光感受器中表达,NCKX2在视锥光感受器和整个大脑的神经元中表达,NCKX3和NCKX4在大脑中含量丰富,但组织分布更广,NCKX5在皮肤、视网膜上皮和大脑中表达。NCKX蛋白可能在调节钠离子浓度广泛且频繁波动环境中的钙离子通量方面发挥特别突出的作用。直到最近,NCKX蛋白所发挥的功能范围总体上仍未得到充分认识。随着越来越多的证据表明其在光感受器适应、突触可塑性和皮肤色素沉着等方面发挥作用,这种情况现在正在迅速改变。CCX(钙/阳离子交换体)分支只有一个哺乳动物成员,即NCKX6或NCLX(钠/钙-锂交换体),尽管其表达模式广泛,但其生理功能仍不清楚。

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