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Review
. 2001 Sep;108(6):779-84.
doi: 10.1172/JCI13992.

LRP: a multifunctional scavenger and signaling receptor

J Herz  1 , D K Strickland
Affiliations
Review

LRP: a multifunctional scavenger and signaling receptor

J Herz et al. J Clin Invest. 2001 Sep.
No abstract available

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Figures

Figure 1
Figure 1
Binding of LRP ligands to the different clusters of ligand-binding repeats. Cysteine-rich ligand-binding repeats (red ovals) in LRP are arranged in four clusters containing 2, 8, 10, and 11 repeats, respectively. Each cluster is followed by 1–4 EGF homology domains (blue), which consist of cysteine-rich EGF repeats (blue circles) and YWTD domains (wavy line). NPxY motifs in the cytoplasmic tail are indicated by the asterisks. No ligand interactions have been mapped to cluster I. Clusters II and IV bind most of the currently mapped known ligands of LRP. Binding of α2M to clusters II and IV has been found by surface plasmon resonance, although cells transfected with minireceptors containing these clusters do not bind and internalize α2M (8). ApoE was found to bind to clusters II, III, and IV by ligand blotting. LPL, lipoprotein lipase.
Figure 2
Figure 2
Extracellular and intracellular associations of LRP with membrane-bound ligands. Left panel: Internalization of GPI-linked or heparan sulfate proteoglycan–linked (HSPG-linked) ligands (examples: uPA:PAI-1, uPA receptor, and apoE-containing lipoproteins). In uPA:PAI-1, PAI-1 binds to LRP and uPA binds to the GPI-linked uPA receptor. ApoE-containing lipoproteins are sequestered on HSPGs, facilitating enrichment with apoE and the interaction with LRP. After internalization and dissociation of the ligands from the receptors in the endosome, receptors recycle to the plasma membrane. Middle panel: Association of LRP with APP mediated by the cytoplasmic scaffolding protein FE65. FE65 can interact via independent PTB domains with the LRP and APP tails. The functional significance of this potential cytoplasmic link for APP processing and/or signaling remains to be shown. Right panel: Dimerization of LRP by α2M and association with NMDA receptors (NMDAR). Dimerization of LRP on cultured neurons induces NMDA receptor–mediated Ca2+ influx. The postsynaptic density protein PSD-95 interacts with LRP and NMDA receptors through different interaction domains. How precisely NMDA receptors are activated by LRP dimerization is not known at present.
See this image and copyright information in PMC

References

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