LRP8
Description
The LRP8 (LDL receptor related protein 8) is a protein-coding gene located on chromosome 1.
Low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), is a protein that in humans is encoded by the LRP8 gene. ApoER2 is a cell surface receptor that is part of the low-density lipoprotein receptor family. These receptors function in signal transduction and endocytosis of specific ligands. Through interactions with one of its ligands, reelin, ApoER2 plays an important role in embryonic neuronal migration and postnatal long-term potentiation. Another LDL family receptor, VLDLR, also interacts with reelin, and together these two receptors influence brain development and function. Decreased expression of ApoER2 is associated with certain neurological diseases.
== Structure == ApoER2 is a protein made up of 870 amino acids. It is separated into a ligand binding domain of eight ligand binding regions, an EGF-like domain containing three cysteine-rich repeats, an O-linked glycosylation domain of 89 amino acids, a transmembrane domain of 24 amino acids, and a cytoplasmic domain of 115 amino acids, including an NPXY motif.
Each letter in the NPXY motif represents a certain amino acid where N is arginine, P is proline, X is any amino acid, and Y is tyrosine.
=== Cytoplasmic tail === All LDL receptor family proteins contain a cytoplasmic tail with at least one NPXY motif.
LRP8 acts as a cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands, playing a crucial role in transmitting the extracellular Reelin signal to intracellular signaling processes by binding to DAB1 on its cytoplasmic tail. Reelin, acting through both the VLDL receptor (VLDLR) and LRP8, regulates DAB1 tyrosine phosphorylation and microtubule function in neurons. LRP8 exhibits a higher affinity for Reelin compared to VLDLR, making it a key component of the Reelin pathway governing neuronal layering of the forebrain during embryonic brain development. LRP8 also binds the endoplasmic reticulum resident receptor-associated protein (RAP) and dimers of beta 2-glycoprotein I, potentially contributing to the suppression of platelet aggregation in the vasculature. Its high expression in the initial segment of the epididymis influences the functional expression of clusterin and phospholipid hydroperoxide glutathione peroxidase (PHGPx), two proteins essential for sperm maturation. LRP8 may also function as an endocytic receptor, although it is not required for the endocytic uptake of SEPP1 in the kidney, which is mediated by LRP2. In collaboration with its ligand, apolipoprotein E (apoE), LRP8 may indirectly suppress the innate immune response by regulating the survival of myeloid-derived suppressor cells.
LRP8 is also known as APOER2, HSZ75190, LRP-8, MCI1.
