Willnow T E, Hilpert J, Armstrong S A, Rohlmann A, Hammer R E, Burns D K, Herz J
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8460-4. doi: 10.1073/pnas.93.16.8460.
gp330/megalin, a member of the low density lipoprotein (LDL) receptor gene family, is expressed on the apical surfaces of epithelial tissues, including the neuroepithelium, where it mediates the endocytic uptake of diverse macromolecules, such as cholesterol-carrying lipoproteins, proteases, and antiproteinases. Megalin knockout mice manifest abnormalities in epithelial tissues including lung and kidney that normally express the protein and they die perinatally from respiratory insufficiency. In brain, impaired proliferation of neuroepithelium produces a holoprosencephalic syndrome, characterized by lack of olfactory bulbs, forebrain fusion, and a common ventricular system. Similar syndromes in humans and animals are caused by insufficient supply of cholesterol during development. Because megalin can bind lipoproteins, we propose that the receptor is part of the maternal-fetal lipoprotein transport system and mediates the endocytic uptake of essential nutrients in the postgastrulation stage.
gp330/megalin是低密度脂蛋白（LDL）受体基因家族的一员，在上皮组织的顶端表面表达，包括神经上皮，在那里它介导多种大分子的内吞摄取，如携带胆固醇的脂蛋白、蛋白酶和抗蛋白酶。Megalin基因敲除小鼠在上皮组织中表现出异常，包括正常表达该蛋白的肺和肾，它们在围产期因呼吸功能不全而死亡。在大脑中，神经上皮增殖受损会产生全前脑综合征，其特征是嗅球缺失、前脑融合和共同的脑室系统。人类和动物的类似综合征是由发育过程中胆固醇供应不足引起的。因为megalin可以结合脂蛋白，我们提出该受体是母胎脂蛋白转运系统的一部分，并在原肠胚形成后期介导必需营养物质的内吞摄取。
