Hirschberg C B, Robbins P W, Abeijon C
Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Massachusetts 02118-2392, USA.
Annu Rev Biochem. 1998;67:49-69. doi: 10.1146/annurev.biochem.67.1.49.
The lumens of the endoplasmic reticulum and Golgi apparatus are the subcellular sites where glycosylation, sulfation, and phosphorylation of secretory and membrane-bound proteins, proteoglycans, and lipids occur. Nucleotide sugars, nucleotide sulfate, and ATP are substrates for these reactions. ATP is also used as an energy source in the lumen of the endoplasmic reticulum during protein folding and degradation. The above nucleotide derivatives and ATP must first be translocated across the membrane of the endoplasmic reticulum and/or Golgi apparatus before they can serve as substrates in the above lumenal reactions. Translocation of the above solutes is mediated for highly specific transporters, which are antiporters with the corresponding nucleoside monophosphates as shown by biochemical and genetic approaches. Mutants in mammals, yeast, and protozoa showed that a defect in a specific translocator activity results in selective impairments of the above posttranslational modifications, including loss of virulence of pathogenic protozoa. Several of these transporters have been purified and cloned. Experiments with yeast and mammalian cells demonstrate that these transporters play a regulatory role in the above reactions. Future studies will address the structure of the above proteins, how they are targeted to different organelles, their potential as drug targets, their role during development, and the possible occurrence of specific diseases.
内质网和高尔基体的管腔是分泌性和膜结合蛋白、蛋白聚糖及脂质进行糖基化、硫酸化和磷酸化的亚细胞位点。核苷酸糖、核苷酸硫酸盐和ATP是这些反应的底物。在蛋白质折叠和降解过程中，ATP还在内质网管腔中用作能量来源。上述核苷酸衍生物和ATP必须首先跨内质网和/或高尔基体膜转运，然后才能作为上述管腔反应的底物。上述溶质的转运由高度特异性的转运蛋白介导，这些转运蛋白是与相应核苷单磷酸形成反向转运体，这已通过生化和遗传学方法得到证实。哺乳动物、酵母和原生动物中的突变体表明，特定转运体活性的缺陷会导致上述翻译后修饰的选择性损伤，包括致病原生动物毒力的丧失。其中几种转运蛋白已被纯化和克隆。对酵母和哺乳动物细胞的实验表明，这些转运蛋白在上述反应中起调节作用。未来的研究将关注上述蛋白质的结构、它们如何靶向不同的细胞器、它们作为药物靶点的潜力、它们在发育过程中的作用以及特定疾病的可能发生情况。
