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: axon; caveola; cell soma; dendrite; extracellular region; integral to membrane; membrane; microtubule associated complex; plasma membrane; postsynaptic density; receptor complex
Molecular Function: apolipoprotein binding; calcium ion binding; high-density lipoprotein binding; kinesin binding; protein binding; transmembrane receptor activity; very-low-density lipoprotein receptor activity
Biological Process: activation of CREB transcription factor; ammon gyrus development; blood coagulation; cytokine and chemokine mediated signaling pathway; endocytosis; fat-soluble vitamin metabolic process; layer formation in the cerebral cortex; lipid metabolic process; negative regulation of transcription from RNA polymerase II promoter; phototransduction, visible light; positive regulation of peptidyl-tyrosine phosphorylation; proteolysis; receptor-mediated endocytosis; regulation of synaptic transmission; response to drug; retinoid metabolic process; signal transduction; vitamin metabolic process
Disease: Myocardial Infarction, Susceptibility To
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