Immunoglobulin heavy chain and binding protein complexes are dissociated in vivo by light chain addition.
Immunoglobulin heavy chain and binding protein complexes are dissociated in vivo by light chain addition.
复制标题
免疫球蛋白重链和结合蛋白络合物通过轻链添加在体内分离。
DOI：
10.1083/jcb.111.3.829
复制
发表时间：
1990-09
影响因子：
7.8
通讯作者：
Hendershot, L M
中科院分区：
文献类型：
--
作者：
Hendershot, L M
免疫球蛋白重链结合蛋白（BiP，GRP78）与Abelson病毒转化的前B细胞系合成的游离、非分泌型IG重链稳定结合。在合成IG重链和轻链的细胞中，IG亚基快速组装并分泌。在这些细胞中，只有不完全组装的IG分子才能与BiP结合。除IG重链外，许多突变和不完全糖基化的转运缺陷蛋白与BiP稳定复合。当检查正常蛋白质与BiP的组合时，可以发现只有一小部分新生的、未折叠的或未组装的蛋白质的细胞内池是相关的。很难确定这些BiP相关分子是否代表将从BiP中置换并从细胞中转运的组装中间体，或者这些是否是最终降解的异常蛋白质。为了使BiP监测和帮助正常的蛋白质转运，它与这些蛋白质的结合必须是可逆的，并且释放的蛋白质应该是有转运能力的。在本文所述的研究中，在产生BiP相关重链的骨髓瘤细胞系和合成互补轻链的骨髓瘤细胞系之间形成了瞬时异核体。轻链合成的引入导致预标记的重链与轻链的组装、BiP从重链的置换以及IG分泌到培养物上清液中。这些数据表明，BiP缔合可以是可逆的，具有可转运蛋白的一致释放。因此，BiP可以被认为是胞外分泌途径的一个组成部分，调节正常和异常蛋白质的转运。
Immunoglobulin heavy chain binding protein (BiP, GRP78) associates stably with the free, nonsecreted Ig heavy chains synthesized by Abelson virus transformed pre-B cell lines. In cells synthesizing both Ig heavy and light chains, the Ig subunits assemble rapidly and are secreted. Only incompletely assembled Ig molecules can be found bound to BiP in these cells. In addition to Ig heavy chains, a number of mutant and incompletely glycosylated transport-defective proteins are stably complexed with BiP. When normal proteins are examined for combination with BiP, only a small fraction of the intracellular pool of nascent, unfolded, or unassembled proteins can be found associated. It has been difficult to determine whether these BiP-associated molecules represent assembly intermediates which will be displaced from BiP and transported from the cell, or whether these are aberrant proteins that are ultimately degraded. In order for BiP to monitor and aid in normal protein transport, its association with these proteins must be reversible and the released proteins should be transport competent. In the studies described here, transient heterokaryons were formed between a myeloma line producing BiP-associated heavy chains and a myeloma line synthesizing the complementary light chain. Introduction of light chain synthesis resulted in assembly of prelabeled heavy chains with light chains, displacement of BiP from heavy chains, and secretion of Ig into the culture supernatant. These data demonstrate that BiP association can be reversible, with concordant release of transportable proteins. Thus, BiP can be considered a component of the exocytic secretory pathway, regulating the transport of both normal and abnormal proteins.