The Departments of Cell Biology, USA.
School of Graduate Studies, USA.
Exp Cell Res. 2020 Nov 1;396(1):112256. doi: 10.1016/j.yexcr.2020.112256. Epub 2020 Sep 6.
Cellular uptake of vitamin B (cobalamin, Cbl) is mediated by a cell surface receptor (TCblR/CD320) that binds transcobalamin (TC) saturated with Cbl. TC is secreted by the vascular endothelium, has a relatively short half-life, binds Cbl with high affinity and presents the vitamin to the receptor for cellular uptake. Here we show binding and internalization of the TC-Cbl complex along with its' receptor (TCblR) in several human cell lines. The expression of TCblR is linked to the cell cycle with highest expression in actively proliferating cells. Upon binding TC-Cbl, the receptors appear to segregate on the plasma membrane and are internalized over the course of 30-60 min. Subsequently, the receptors appear to be destroyed along with the TC, which results in the release of free Cbl in the lysosome. The appearance of TCblR on the cell surface is limited to newly synthesized protein without contribution from recycling of the receptor. Therefore, Cbl uptake into cells is fully dependent on the expression of newly synthesized TCblR that is up-regulated in actively proliferating cells. The cell cycle-associated up-regulation of TCblR in cancers provides a route for targeted drug delivery.
细胞对维生素 B（钴胺素，Cbl）的摄取是由细胞表面受体（TCblR/CD320）介导的，该受体结合了与 Cbl 饱和的转钴胺素（TC）。TC 由血管内皮细胞分泌，半衰期相对较短，与 Cbl 具有高亲和力，并将维生素呈现给受体进行细胞摄取。在这里，我们展示了几种人类细胞系中 TC-Cbl 复合物及其受体（TCblR）的结合和内化。TCblR 的表达与细胞周期相关，在活跃增殖的细胞中表达最高。在结合 TC-Cbl 后，受体似乎在质膜上隔离，并在 30-60 分钟内内化。随后，受体似乎与 TC 一起被破坏，导致溶酶体中游离 Cbl 的释放。TCblR 出现在细胞表面仅限于新合成的蛋白质，而不依赖于受体的循环利用。因此，Cbl 进入细胞的摄取完全依赖于新合成的 TCblR 的表达，而 TCblR 在活跃增殖的细胞中上调。癌症中与细胞周期相关的 TCblR 上调为靶向药物输送提供了一种途径。
