Low-density lipoprotein receptor-related protein 8 (UniProt Q924X6; also known as ApoER2, Apolipoprotein E receptor 2, LRP-8) is encoded by the Lrp8 (also known as Apoer2) gene (Gene ID 16975) in murine species. Murine ApoER2/LRP-8 is an 110-kDa type I membrane receptor initially produced with a signal peptide sequence (a.a.1-28). The mature receptor has a large extracellular region (a.a. 29-858), a transmembrane domain (a.a. 859-881), and a cytoplasmic tail (a.a. 882-996). ApoER2 belongs to the LDLR family of membrane glycoproteins whose members also inculde the low-density lipoprotein receptor (LDLR), the very-low-density lipoprotein (VLDL) receptor, the LDLR-related protein (LRP), and Megalin (LRP-2). The overall extracellular structural features are similar among all LDLR family members. ApoER2 contains a cluster of eight cysteine-rich Complement-type/LDLR Class A repeats that mediate ligand-binding, followed by two EGF-like repeats (a.a. 364-408 & 409-448) and a cluster of five cysteine-poor LDLR Class B repeats (a.a. 495-714) that contains YWTD motifs involved in the pH-dependent ligands dissociation in endosomal compartments. ApoER2 and VLDLR both function as receptor for reelin, a glycoprotein that is mainly secreted by Cajal Retzius neurons in the marginal zone and plays an essential role in the formation of the layered neocortex. Immunohistochemical staining reveals differential localization of ApoER2 and VLDLR in the developing mouse cerebral cortex, with VLDLR being localized to the distal portion of leading processes in the marginal zone (MZ) and ApoER2 mainly localized to neuronal processes and the cell membranes of multipolar cells in the multipolar cell accumulation zone (MAZ). The differential expression pattern may therefore allow distinct reelin actions on migrating neurons during both the early and late migratory stages in the developing cerebral cortex.
Synonyms: Low-density lipoprotein receptor-related protein 8, ApoER2, Apolipoprotein E receptor 2, LRP-8
Application: Research CategoryNeuroscience
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