Identification and functional analysis of the LDL receptor gene family members

点击翻译按钮获取中文摘要

Receptors belonging to the LDL receptor gene family are playing key roles for wide varied species in cellular endocytosis of a broad spectrum of ligands including spent, biologically inactive and/or unwanted plasmatic carrier complexes, certain toxins, yolk precursors, as well as circulating plasma lipoproteins. We now have discovered and characterized a novel multidomain protein and classified it as a member of the LDL receptor gene family. The -250kDa membrane protein, termed LR11, contains a cluster of 11 LDL receptor ligand binding repeats, a rgoup of 5 LDL receptor "YWTD" repeats, a large hexarepeat domain of structural elements found in neural cell adhesion molecules, and a domain with similarity to a yeast receptor for vacuolar protein sorting, VPS10. The cytoplasmic domain exhibits features typical of endocytosis-competent coated-pit receptors. The mosaic, and presumably multifunctional, receptor is expressed abundantly in brain, liver and adrenal glands. Ligand blotting of LR11-transfected cells demonstrated that LR11 binds apolipoproteinE-containing lipoproteins, as well as other members of LDL receptor gene family. In contrast to the LDL receptor, the mRNA levels in rabbit liver is unaffected by hyperlipidemia. At present, we have no idea which ligand (s) may be the true physiological partner (s) of LR11. However, the localization of rabbit LR11 in the hippocampus, dentate gyrus and cerebral cortex suggests functional significance of LR11 in metabolically active regions of brain. The novel complex mosaic structure of LR11 sheds new lights on the evolution and proposed multifunctionality of the LDLR gene family.