LRP8: Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands. LRP8 participates in transmitting the extracellular Reelin signal to intracellular signaling processes, by binding to DAB1 on its cytoplasmic tail. Reelin acts via both the VLDL receptor (VLDLR) and LRP8 to regulate DAB1 tyrosine phosphorylation and microtubule function in neurons. LRP8 has higher affinity for Reelin than VLDLR. LRP8 is thus a key component of the Reelin pathway which governs neuronal layering of the forebrain during embryonic brain development. Binds the endoplasmic reticulum resident receptor-associated protein (RAP). Binds dimers of beta 2-glycoprotein I and may be involved in the suppression of platelet aggregation in the vasculature. Highly expressed in the initial segment of the epididymis, where it affects the functional expression of clusterin and phospholipid hydroperoxide glutathione peroxidase (PHGPx), two proteins required for sperm maturation. May also function as an endocytic receptor. Defects in LRP8 are a cause of myocardial infarction type 1 (MCI1). A condition defined by the irreversible necrosis of heart muscle secondary to prolonged ischemia. Belongs to the LDLR family. 5 isoforms of the human protein are produced by alternative splicing.
Protein type: Receptor, misc.; Membrane protein, integral
Chromosomal Location of Human Ortholog: 1p34
Cellular Component: microtubule associated complex; membrane; cell soma; axon; dendrite; postsynaptic density; extracellular region; integral to membrane; plasma membrane; caveola; receptor complex
Molecular Function: very-low-density lipoprotein receptor activity; protein binding; transmembrane receptor activity; kinesin binding; apolipoprotein binding; calcium ion binding; high-density lipoprotein binding
Biological Process: regulation of synaptic transmission; response to drug; receptor-mediated endocytosis; phototransduction, visible light; cytokine and chemokine mediated signaling pathway; activation of CREB transcription factor; endocytosis; negative regulation of transcription from RNA polymerase II promoter; signal transduction; proteolysis; ammon gyrus development; positive regulation of peptidyl-tyrosine phosphorylation; lipid metabolic process; retinoid metabolic process; blood coagulation; layer formation in the cerebral cortex
Disease: Myocardial Infarction, Susceptibility To
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