CD91, low density lipoprotein (LDL) receptor related protein (LRP) 1, apolipoprotein E [apoE] receptor 1, chylomicron remnant receptor or alpha-2 macroglobulin receptor
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Function
- endocytic receptor involved in endocytosis & in phagocytosis of apoptotic cells
- required for early embryonic development
- involved in cellular lipid homeostasis
- involved in plasma clearance of chylomicron remnants & activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators & their endogenous inhibitors
- may modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal Ca+2 signaling as well as neurotransmission
- intracellular domain interacts with MAFB (putative)
- found in a complex with PID1/PCLI1, LRP1 & CUBNI
- interacts with SNX17, PID1/PCLI1, PDGF & CUBN
- the intracellular domain interacts with SHC1, GULP1 & DAB1
- interacts with LRPAP1
- gamma-secretase-dependent cleavage of LRP-85 releases the intracellular domain from the membrane
- phosphorylated on Ser & Thr
- phosphorylated on Tyr upon stimulation with PDGF
- Tyr phosphorylation promotes interaction with SHC1
- LRP1 binds 30 different ligands, including:
- LRP1 associates with cell-surface proteoglycan, which serves to non-specifically bind proteins & present them for specific binding to the receptor LRP1
- LRP1 associates with p39RAP that modifies binding of ligands to the LRP1-alpha
- LRP1 binds ApoE*
- LRP also binds & internalizes the protease/protease-inhibitor complex of alpha-2 macroglobulin
- the receptor alpha-2 macroglobulin complex may be involved in clearance of proteases & other proteins
Structure
- heterodimer of an 85-kD membrane-bound carboxyl subunit & a non-covalently attached 515-kD amino-terminal subunit derived from a 4544 amino acid precursor (see LRP1 precursor)
- contains 31 complement repeats & 22 growth factor repeats
- the N-terminus is blocked
- homologous to the LDL receptor
Compartment
- cell membrane, coated pit
- after cleavage, the intracellular domain (LRPICD) is detected both in the cytoplasm & in the nucleus
Expression
- most abundant in liver, brain & lung
- highest expression of LRP1 is in liver
- expressed in brain
- expressed on brain capillaries
- binding of alpha-2 macroglobulin associated with Ca+2 influx through the NMDA receptor
- lung
- fibroblasts
- dendritic cells
- macrophages
Pathology
- hepatic LRP1 binds apo E3 & apo E4, but not apo E2;[8] thus homozygous apo E2 is associated with dysbetalipoproteinemia (Frederickson type 3 hyperlipoproteinemia)
More general terms
Additional terms
- alpha-2-macroglobulin receptor-associated protein; alpha-2-MRAP; low density lipoprotein receptor-related protein-associated protein 1; RAP; p39RAP (LRPAP1, A2MRAP)
- alpha-2-macroglobulin; alpha-2-M; C3 & PZP-like alpha-2-macroglobulin domain-containing protein 5 (A2M, CPAMD5, FWP007)
- apolipoprotein E (APOE)
- chylomicron
- hyperlipoproteinemia type 3; familial dysbetalipoproteinemia; remnant hyperlipidemia; remnant hyperlipoproteinaemia; broad beta disease; remnant removal disease
- intermediate density lipoprotein (IDL) or VLDL remnant
- low density lipoprotein (LDL) receptor related protein (LRP) 2 (LRP2, glycoprotein 330, gp330)
- low-density lipoprotein receptor; LDL receptor; apoB/E receptor (LDLR)
- proteoglycan
References
- ↑ Primary Hyperlipoproteinemias, Steiner & Shafrir (eds), McGraw Hill, NY, 1991, pg 32
- ↑ Beisiegel et al Nature 341(6238):162-4, 1989
- ↑ Descamps et al J Biol Chem 268(2):974-81, 1993
- ↑ Wolf et al Am J Pathol 141:37 1992
- ↑ Williams et al J Biol Chem 267:9035 1992
- ↑ Herz et al EMBO J 7:4199 1988
- ↑ Strickland et al J Biol Chem 265:17401 1990
- ↑ 8.0 8.1 Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA & Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993, pg 1025
- ↑ Herz & Strickland J Cin Invest 108:779, 2001
- ↑ 10.0 10.1 Rebeck et al Molecular Brain Res 87: 238, 2001
- ↑ http://www.pathologyoutlines.com/cdmarkers.html 4 May 2004
- ↑ 12.0 12.1 Sagare A et al, Clearance of amyloid-beta by circulating lipoprotein receptors Nat Med 2007, 13:1029 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17694066