Borén J, White A, Wettesten M, Scott J, Graham L, Olofsson S O
Department of Medical Biochemistry, University of Göteborg, Sweden.
Prog Lipid Res. 1991;30(2-3):205-18. doi: 10.1016/0163-7827(91)90017-y.
We have reviewed the literature on the intracellular transport of ApoB-100 and the assembly of the ApoB-100-containing lipoproteins. ApoB-100 is a large molecule (4536 aa) that requires some 15 min to be completed. During the synthesis, the protein could take one of two pathways: a degradational pathway and a pathway that leads to secretion of the protein on mature lipoproteins. The degradational pathway starts with a cotranslational incorporation of ApoB-100 into the membrane of the endoplasmic reticulum in such a way that a relatively large portion of the sequence is exposed on the cytoplasmic surface of this membrane. The membrane bound ApoB-100 is retained in the ER and will eventually undergo intracellular degradation. To enter the pathway that leads to lipoprotein formation, ApoB-100 has to be cotranslationally translocated to the lumen of the ER. ApoB-100 will interact with the lipids during this translation-translocation process and the mature lipoprotein is released into the lumen of the secretory pathway when ApoB-100 is completed and leaves the ribosome. In addition to the mature lipoproteins, the secretory pathway contains an ApoB-100-containing lipoprotein with the density of a HDL particle. This particle is not secreted from the cells but is retained and eventually degraded. Of importance for the retention are sequences present in the C-terminal half of the protein. The mature lipoproteins rapidly leave the ER lumen and are transported to the Golgi apparatus, through which transfer takes considerably longer. The assembly process is a potential site for the regulation of the secretion of the ApoB-100-containing lipoproteins. This process is dependent on active synthesis of phosphatidylcholine and it is also highly dependent on the rate of triacylglycerol synthesis. On the other hand, ApoB-100 appears to be constitutively expressed. An increase in the rate of lipoprotein assembly induced by an increased triacylglycerol synthesis gives rise to an increased recruitment of ApoB-100 nascent polypeptides to interact cotranslationally with lipids. ApoB-100 that is not used for lipoprotein assembly is cotranslationally bound to the ER membrane and sorted to degradation.
我们回顾了有关载脂蛋白B-100（ApoB-100）细胞内运输及含ApoB-100脂蛋白组装的文献。ApoB-100是一个大分子（4536个氨基酸），合成大约需要15分钟。在合成过程中，该蛋白质可能走两条途径之一：一条降解途径和一条导致蛋白质分泌到成熟脂蛋白上的途径。降解途径始于ApoB-100共翻译插入内质网的膜中，使得相当一部分序列暴露在该膜的细胞质表面。结合在膜上的ApoB-100保留在内质网中，最终会经历细胞内降解。为了进入导致脂蛋白形成的途径，ApoB-100必须共翻译转运到内质网腔中。在这个翻译-转运过程中，ApoB-100会与脂质相互作用，当ApoB-100合成完成并离开核糖体时，成熟脂蛋白被释放到分泌途径的腔中。除了成熟脂蛋白外，分泌途径还包含一种密度与高密度脂蛋白（HDL）颗粒相同的含ApoB-100脂蛋白。这种颗粒不会从细胞中分泌出来，而是被保留并最终降解。对于这种保留很重要的是蛋白质C末端一半中存在的序列。成熟脂蛋白迅速离开内质网腔并被转运到高尔基体，通过高尔基体的转运所需时间长得多。组装过程是调节含ApoB-100脂蛋白分泌的一个潜在位点。这个过程依赖于磷脂酰胆碱的活跃合成，并且也高度依赖于三酰甘油的合成速率。另一方面，ApoB-100似乎是组成性表达的。三酰甘油合成增加诱导的脂蛋白组装速率增加，会导致更多的ApoB-100新生多肽共翻译与脂质相互作用。未用于脂蛋白组装的ApoB-100共翻译结合在内质网膜上并被分类进行降解。
