Yochem J, Tuck S, Greenwald I, Han M
Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 USA.
Development. 1999 Feb;126(3):597-606. doi: 10.1242/dev.126.3.597.
A genetic analysis of a gp330/megalin-related protein, LRP-1, has been undertaken in Caenorhabditis elegans. Consistent with megalin's being essential for development of mice, likely null mutations reveal that this large member of the low density lipoprotein receptor family is also essential for growth and development of this nematode. The mutations confer a striking defect, an inability to shed and degrade all of the old cuticle at each of the larval molts. The mutations also cause an arrest of growth usually at the molt from the third to the fourth larval stage. Genetic mosaic analysis suggests that the lrp-1 gene functions in the major epidermal syncytium hyp7, a polarized epithelium that secretes cuticle from its apical surface. Staining of whole mounts with specific monoclonal antibodies reveals that the protein is expressed on the apical surface of hyp7. Sterol starvation can phenocopy the lrp-1 mutations, suggesting that LRP-1 is a receptor for sterols that must be endocytosed by hyp7. These observations indicate that LRP-1 is related to megalin not only structurally but also functionally.
已对秀丽隐杆线虫中的一种与gp330/巨蛋白相关的蛋白质LRP-1进行了基因分析。与巨蛋白对小鼠发育至关重要一致，可能的无效突变表明，低密度脂蛋白受体家族的这个大成员对该线虫的生长和发育也至关重要。这些突变导致一个显著缺陷，即无法在每次幼虫蜕皮时蜕去并降解所有旧表皮。这些突变通常还会导致在从第三幼虫阶段到第四幼虫阶段的蜕皮时生长停滞。基因镶嵌分析表明，lrp-1基因在主要的表皮合胞体hyp7中发挥作用，hyp7是一种极化上皮，从其顶端表面分泌表皮。用特异性单克隆抗体对整装标本进行染色显示，该蛋白在hyp7的顶端表面表达。固醇饥饿可模拟lrp-1突变，表明LRP-1是一种固醇受体，必须被hyp7内吞。这些观察结果表明，LRP-1不仅在结构上而且在功能上与巨蛋白相关。
