Reactome | LRP2-mediated TCN2:RCbl uptake and delivery to lysosome

LRP2-mediated TCN2:RCbl uptake and delivery to lysosome

Stable Identifier

R-HSA-9759202

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

lysosomal lumen, plasma membrane

ReviewStatus

5/5

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LRP2-mediated TCN2:RCbl uptake and delivery to lysosome

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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 Nagai, M, Meerloo, T, Takeda, T, Farquhar, MG	Mol Biol Cell	2003
7768901	Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin Kounnas, MZ, Loukinova, EB, Stefansson, S, Harmony, JA, Brewer, BH, 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 Hjalm, G, Murray, E, Crumley, G, Harazim, W, Lundgren, S, Onyango, I, Ek, B, Larsson, M, Juhlin, C, Hellman, P, Davis, H, Akerstrom, G, Rask, L, Morse, B	Eur J Biochem	1996
23836931	ARH directs megalin to the endocytic recycling compartment to regulate its proteolysis and gene expression Shah, M, Baterina, OY, Taupin, V, Farquhar, MG	J Cell Biol	2013
8710919	Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis Moestrup, SK, Birn, H, Fischer, PB, Petersen, CM, Verroust, PJ, Sim, RB, Christensen, EI, Nexø, E	Proc Natl Acad Sci U S A	1996