The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.
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DOI：
10.1042/bj3430281
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发表时间：
1999-10
期刊：
影响因子：
--
通讯作者：
A. Halestrap;N. Price
中科院分区：
文献类型：
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作者：
A. Halestrap;N. Price
单羧酸盐如乳酸盐和丙酮酸盐在细胞代谢和组织间代谢通讯中起着重要作用。这些作用的关键是它们快速跨质膜转运，这是由最近发现的质子连接单羧酸转运蛋白（MCT）家族催化的。到目前为止，已经在哺乳动物中确定了9个MCT相关序列，每个序列具有不同的组织分布，而6个相关蛋白质可以在秀丽隐杆线虫中识别，4个在酿酒酵母中识别。已在哺乳动物MCT 1-MCT 4中直接证明了质子连接的乳酸盐和丙酮酸盐转运，但仅对MCT 1和MCT 2在非洲爪蟾卵母细胞中异源表达后的底物和抑制剂动力学进行了详细分析。MCT 1广泛表达，但在心脏和红肌中尤其突出，在那里它响应于增加的工作而上调，表明在乳酸氧化中的特殊作用。相比之下，MCT 4在白色肌肉和其他具有高糖酵解速率的细胞中最明显，例如肿瘤细胞和白色血细胞，表明其在乳酸流出占主导地位的地方表达。MCT 2对底物的亲和力比MCT 1和MCT 4高10倍，并且在可能需要在低底物浓度下快速摄取的细胞中发现，包括近端肾小管、神经元和精子尾部。MCT 3在视网膜色素上皮中唯一表达。参与调节不同MCT亚型表达的机制仍有待建立。然而，有证据表明5 '-和3'-非翻译区的选择性剪接以及某些同种型使用选择性启动子。此外，MCT 1和MCT 4已显示与OX-47（CD 147）特异性相互作用，OX-47是具有单个跨膜螺旋的免疫球蛋白超家族成员。这种相互作用似乎有助于MCT在细胞表面的表达。仍有许多工作要做，以表征不同亚型的特性及其调节，这可能对健康和疾病产生广泛的影响。将来，通过染色体定位探索遗传疾病与特定MCT的联系将是有趣的。
Monocarboxylates such as lactate and pyruvate play a central role in cellular metabolism and metabolic communication between tissues. Essential to these roles is their rapid transport across the plasma membrane, which is catalysed by a recently identified family of proton-linked monocarboxylate transporters (MCTs). Nine MCT-related sequences have so far been identified in mammals, each having a different tissue distribution, whereas six related proteins can be recognized in Caenorhabditis elegans and 4 in Saccharomyces cerevisiae. Direct demonstration of proton-linked lactate and pyruvate transport has been demonstrated for mammalian MCT1-MCT4, but only for MCT1 and MCT2 have detailed analyses of substrate and inhibitor kinetics been described following heterologous expression in Xenopus oocytes. MCT1 is ubiquitously expressed, but is especially prominent in heart and red muscle, where it is up-regulated in response to increased work, suggesting a special role in lactic acid oxidation. By contrast, MCT4 is most evident in white muscle and other cells with a high glycolytic rate, such as tumour cells and white blood cells, suggesting it is expressed where lactic acid efflux predominates. MCT2 has a ten-fold higher affinity for substrates than MCT1 and MCT4 and is found in cells where rapid uptake at low substrate concentrations may be required, including the proximal kidney tubules, neurons and sperm tails. MCT3 is uniquely expressed in the retinal pigment epithelium. The mechanisms involved in regulating the expression of different MCT isoforms remain to be established. However, there is evidence for alternative splicing of the 5'- and 3'-untranslated regions and the use of alternative promoters for some isoforms. In addition, MCT1 and MCT4 have been shown to interact specifically with OX-47 (CD147), a member of the immunoglobulin superfamily with a single transmembrane helix. This interaction appears to assist MCT expression at the cell surface. There is still much work to be done to characterize the properties of the different isoforms and their regulation, which may have wide-ranging implications for health and disease. In the future it will be interesting to explore the linkage of genetic diseases to particular MCTs through their chromosomal location.