Hediger M A, Kanai Y, You G, Nussberger S
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Physiol. 1995 Jan;482(P):7S-17S. doi: 10.1113/jphysiol.1995.sp020559.
Active transport of solutes into and out of cells proceeds via specialized transporters that utilize diverse energy-coupling mechanisms. Ion-coupled transporters link uphill solute transport to downhill electrochemical ion gradients. In mammals, these transporters are coupled to the co-transport of H+, Na+, Cl- and/or to the countertransport of K+ or OH-. By contrast, ATP-dependent transporters are directly energized by the hydrolysis of ATP. The development of expression cloning approaches to select cDNA clones solely based on their capacity to induce transport function in Xenopus oocytes has led to the cloning of several ion-coupled transporter cDNAs and revealed new insights into structural designs, energy-coupling mechanisms and physiological relevance of the transporter proteins. Different types of mammalian ion-coupled transporters are illustrated by discussing transporters isolated in our own laboratory such as the Na+/glucose co-transporters SGLT1 and SGLT2, the H(+)-coupled oligopeptide transporters PepT1 and PepT2, and the Na(+)- and K(+)-dependent neuronal and epithelial high affinity glutamate transporter EAAC1. Most mammalian ion-coupled organic solute transporters studied so far can be grouped into the following transporter families: (1) the predominantly Na(+)-coupled transporter family which includes the Na+/glucose co-transporters SGLT1, SGLT2, SGLT3 (SAAT-pSGLT2) and the inositol transporter SMIT, (2) the Na(+)- and Cl(-)-coupled transporter family which includes the neurotransmitter transporters of gamma-amino-butyric acid (GABA), serotonin, dopamine, norepinephrine, glycine and proline as well as transporters of beta-amino acids, (3) the Na(+)- and K(+)-dependent glutamate/neurotransmitter family which includes the high affinity glutamate transporters EAAC1, GLT-1, GLAST, EAAT4 and the neutral amino acid transporters ASCT1 and SATT1 reminiscent of system ASC and (4) the H(+)-coupled oligopeptide transporter family which includes the intestinal H(+)-dependent oligopeptide transporter PepT1.
溶质进出细胞的主动运输是通过利用多种能量偶联机制的特殊转运体进行的。离子偶联转运体将溶质的上坡运输与下坡电化学离子梯度联系起来。在哺乳动物中，这些转运体与H⁺、Na⁺、Cl⁻的协同运输或K⁺或OH⁻的反向运输偶联。相比之下，ATP依赖性转运体直接由ATP水解提供能量。仅基于其在非洲爪蟾卵母细胞中诱导运输功能的能力来选择cDNA克隆的表达克隆方法的发展，导致了几种离子偶联转运体cDNA的克隆，并揭示了对转运体蛋白的结构设计、能量偶联机制和生理相关性的新见解。通过讨论在我们自己实验室中分离的转运体，如Na⁺/葡萄糖协同转运体SGLT1和SGLT2、H⁺偶联寡肽转运体PepT1和PepT2以及Na⁺和K⁺依赖性神经元和上皮高亲和力谷氨酸转运体EAAC1，来说明不同类型的哺乳动物离子偶联转运体。到目前为止，研究的大多数哺乳动物离子偶联有机溶质转运体可以分为以下转运体家族：(1)主要为Na⁺偶联的转运体家族，包括Na⁺/葡萄糖协同转运体SGLT1、SGLT2、SGLT3(SAAT-pSGLT2)和肌醇转运体SMIT；(2)Na⁺和Cl⁻偶联的转运体家族，包括γ-氨基丁酸(GABA)、5-羟色胺、多巴胺、去甲肾上腺素、甘氨酸和脯氨酸的神经递质转运体以及β-氨基酸转运体；(3)Na⁺和K⁺依赖性谷氨酸/神经递质家族，包括高亲和力谷氨酸转运体EAAC1、GLT-1、GLAST、EAAT4和让人联想到系统ASC的中性氨基酸转运体ASCT1和SATT1；(4)H⁺偶联寡肽转运体家族，包括肠道H⁺依赖性寡肽转运体PepT1。
