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.
Takeda, T, Meerloo, T, Nagai, M, Farquhar, MG
Brewer, BH, Stefansson, S, Harmony, JA, Loukinova, EB, Kounnas, MZ, Strickland, DK, Argraves, WS
Lundgren, S, Murray, E, Larsson, M, Crumley, G, Hellman, P, Akerstrom, G, Juhlin, C, Ek, B, Morse, B, Davis, H, Rask, L, Onyango, I, Harazim, W, Hjalm, G
Taupin, V, Shah, M, Farquhar, MG, Baterina, OY
Verroust, PJ, Birn, H, Sim, RB, Moestrup, SK, Christensen, EI, Fischer, PB, Nexø, E, Petersen, CM
cargo receptor activity of LRP2:LDLRAP1:TCN2:RCbl [plasma membrane]
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