LRP2-mediated TCN2:RCbl uptake and delivery to lysosome

The complex of plasma membrane-associated LRP2 (megalin, glycoprotein 330) and LDLRAP1 (Low density lipoprotein receptor adapter protein 1, also known as ARH, Autosomal recessive hypercholesterolemia protein) bound to transcobalamin2 complexed with cobalamins (TCN2:RCbl) is endocytosed into clathrin-coated vesicles (Nagai et al. 2003). LRP2:LDLRAP1 then dissociates from TCN2:RCbl and returns to the plasma membrane (Shah et al. 2013) while TCN2:RCbl is targeted to lysosomes where TCN2 is degraded and RCbl is released. LRP2, a member of the low density lipoprotein receptor family, is present in renal proximal tubule epithelial cells (Kounnas et al. 1995, Hjalm et al. 1996, Moestrup et al. 1996). This process both prevents loss of RCbl into the urine and preserves the pool of free RCbl in kidney cells that is used to maintain normal levels of RCbl in the body.

质膜结合的LRP2（巨淋，糖蛋白330，亦称megalin）与LDLRAP1（低密度脂蛋白受体适配蛋白1，又称ARH，常染色体隐性高胆固醇血症蛋白）形成的复合物与 transcobalamin2 结合的钴胺素复合物（TCN2:RCbl）被内吞入网格蛋白包被的囊泡中（Nagai 等，2003年）。LRP2:LDLRAP1随后从TCN2:RCbl解离，并返回到质膜（Shah 等，2013年），而TCN2:RCbl则被靶向至溶酶体，其中TCN2被降解，RCbl被释放。LRP2，低密度脂蛋白受体家族成员，存在于肾近端肾小管上皮细胞中（Kounnas 等，1995年，Hjalm 等，1996年，Moestrup 等，1996年）。此过程既防止RCbl进入尿液，又维持肾脏细胞中游离RCbl的库，以保持体内RCbl的正常水平。