Cellular uptake of vitamin B₁₂ (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.

维生素B ₁₂（钴胺素，Cbl）的细胞摄取是由细胞表面受体（TCblR / CD320）介导的）结合用Cbl饱和的反钴胺素（TC）。TC由血管内皮分泌，具有相对较短的半衰期，以高亲和力结合Cbl，并将维生素提供给细胞吸收受体。在这里，我们显示了TC-Cbl复合物及其受体（TCblR）在几种人类细胞系中的结合和内在化。TCblR的表达与活跃增殖细胞中表达最高的细胞周期有关。结合TC-Cbl后，受体似乎在质膜上分离并在30-60分钟内被内在化。随后，受体似乎与TC一起被破坏，这导致溶酶体中游离Cbl的释放。TCblR在细胞表面的出现仅限于新合成的蛋白质，而没有受体循环的作用。因此，Cbl摄取到细胞中完全取决于新合成的TCblR的表达，该表达在活跃增殖的细胞中被上调。细胞周期相关的TCblR在癌症中的上调提供了靶向药物递送的途径。