1988 Discovery of the LDL receptor-related protein (LRP). One of the largest membrane proteins to date, LRP was found using a homology screening approach against the most conserved sequences in the LDL receptor ligand binding domain. Because of its striking structural similarity to the LDL receptor, in particular the presence of 4 highly conserved ligand binding domains, LRP was proposed to function as a hypothetical chylomicron remnant receptor that, in concert with the LDL receptor, was thought to mediate the removal of dietary cholesterol by the liver.
1989 LRP functions as a receptor for ApoE in vitro and cultured cells.
1992 Disruption of the LRP gene in the mouse by homologous recombination reveals an essential function during embryonic development.
1993 Recombinant adenovirus can serve as an efficient gene transfer vehicle for overexpression of the LDL receptor in mouse liver.
1993 Generation of LDL receptor-deficient mice as a small animal model of human hypercholesterolemia. Recombinant adenovirus corrects LDL receptor deficiency in knockout mice.
1994 Gene transfer of an endogenous inhibitor of ligand binding to LRP using recombinant adenovirus results in the accumulation of remnant lipoproteins in the circulation of LDL receptor knockout mice.
1995 Genetic disruption of RAP, a molecular chaperone for LRP, results in impaired production of LRP and a related receptor, megalin.
1996 Genetic disruption of the LDL receptor family member megalin causes holoprosencephaly, a frequent genetic malformation of human newborns.
1998 Definitive evidence for a function of LRP as a chylomicron remnant receptor was obtained in genetically altered mice in which LRP could be conditionally inactivated in the liver.
1998 A class of cytoplasmic adaptor proteins containing PTB protein interaction domains is shown to interact with the cytoplasmic tail of LDL receptor family members and the amyloid precursor protein.
1999 Reelin directly binds to VLDLR and ApoER2/LRP8 to regulate Disabled 1(Dab1) tyrosine phosphorylation and microtubule function in neurons.
2002 Tyrosine phosphorylation of LRP occurs in caveolae and requires the platelet-derived growth factor (PDGF) receptor beta and phosphoinositide 3-kinase.
2002 VLDLR or ApoER2/LRP8 are necessary for Reelin-dependent enhancement of synaptic transmission in the hippocampus.
2002 Activation of phosphoinositide 3-kinase, protein kinase B, and inhibition of glycogen synthase kinase 3β is downstream of Reelin signaling.
2003 Autosomal recessive hypercholesterolemia plays a critical role in LDLR endocytosis in the liver.
2004 Regulation of neuronal migration and synaptic transmission is mediated by synergistic Reelin and Cdk5 parallel pathways in the developing and mature brain.
2004 Reelin treatment targets Dab1 for proteolytic degradation by the ubiquitin-proteasome pathway meditated by VLDLR and ApoER2/LRP8.
2004 LRP is associated with Postsynaptic Proteins and regulates motor function.
2005 LRP1 modulated PDGF signaling by controlling ubiquitination and endocytosis of the PDGFR.
2005 Alternative splicing of Apoer2 modulates Reelin-dependent NMDA receptor activity, synaptic neurotransmission, and memory.
2007 Enhanced activation of TGFβ signaling in LRP1-deficient vascular wall.
2009 LRP1 regulates cellular proliferation and vascular wall integrity by mediating cPLA2 activation and ABCA1 expression.
2009 LRP1 regulates actin organization and cell migration through PDGFRβ-dependent activation of PI3K.
2009 Reelin protects against Aβ-induced suppression of long-term potentiation in ex vivo brain slices.
2010 ApoE4 impairs both ApoE receptor and glutamate receptor recycling – Reelin resistance.
2013 Neuromuscular junction formation and function are mediated by the cross-talk between APP, LRP4, and Agrin.
2014 ApoE receptor Apoer2 plays a key role in synaptic plasticity and fear learning, which is mediated by differential splicing and glycosylation.
2015 Lrp4 differentially regulates limb/brain development and synaptic plasticity.
2015 Reelin-depleted mice are more susceptible to Aβ-induced synaptic dysfunction and memory impairments.
2016 ApoE levels in the hippocampus are altered in ApoE3-KI mice and not in ApoE4-KI mice on a high-fat diet, while the ketogenic diet does not alter hippocampal ApoE in both ApoE3-KI and ApoE4-KI mice.
2016 Reelin-depletion protects against Ldlr-KO-induced atherosclerosis by reducing leukocyte-endothelial cell adhesion.
2016 LRP1 deficiency causes metabolic disruption: hepatic insulin resistance, dyslipidemia, and hepatic steatosis.
2016 Restoring ApoE levels in plasma improved cognition and synaptic function in ApoE-deficient mice.
2017 Altered lipidomic and transcriptomics in progranulin-deficient mice.
2017 Phosphorylation of LRP1 protects against atherosclerosis.
2018 Depletion and inhibition of early endosomal Sodium/Hydrogen exchanger 6 (NHE6) restores ApoE4-induced Reelin resistance and synaptic dysfunction.
2020 Reelin depletion plays a protective role in a mouse model of multiple sclerosis.
2021 Reelin depletion reduces vascular adhesion of leukocytes thus protecting against atherosclerosis.
2021 Reelin/ApoE receptor Apoer2 deletion protects against a mouse model of multiple sclerosis by reducing endothelial adhesion of monocytes.
2021 Reelin plays a role in long-term depression through STEP61 and calcium-permeable AMPA receptors in adulthood.
2021 Early endosomal Sodium/Hydrogen exchanger 6 (NHE6) depletion substantially reduces Aβ plaque deposition and corrects ApoE4-mediated synaptic dysfunction.