LRP2-mediated TCN2:RCbl uptake and delivery to lysosome

Stable Identifier
Reaction [omitted]
Homo sapiens
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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.
Literature References
PubMed ID Title Journal Year
14528014 The adaptor protein ARH escorts megalin to and through endosomes

Takeda, T, Meerloo, T, Nagai, M, Farquhar, MG

Mol Biol Cell 2003
7768901 Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin

Brewer, BH, Stefansson, S, Harmony, JA, Loukinova, EB, Kounnas, MZ, Strickland, DK, Argraves, WS

J Biol Chem 1995
8706697 Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties

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

Eur J Biochem 1996
23836931 ARH directs megalin to the endocytic recycling compartment to regulate its proteolysis and gene expression

Taupin, V, Shah, M, Farquhar, MG, Baterina, OY

J Cell Biol 2013
8710919 Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis

Verroust, PJ, Birn, H, Sim, RB, Moestrup, SK, Christensen, EI, Fischer, PB, Nexø, E, Petersen, CM

Proc Natl Acad Sci U S A 1996
Catalyst Activity

cargo receptor activity of LRP2:LDLRAP1:TCN2:RCbl [plasma membrane]

Orthologous Events
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