Tolleshaug H, Hobgood K K, Brown M S, Goldstein J L
Cell. 1983 Mar;32(3):941-51. doi: 10.1016/0092-8674(83)90079-x.
The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. We describe seven mutations that disrupt synthesis, processing and transport of the receptor in fibroblasts from 77 subjects with the clinical diagnosis of homozygous familial hypercholesterolemia. One mutation obliterates synthesis of immunoprecipitable precursor. Three mutations specify precursors (100, 120 and 135 kd) that fail to undergo normal processing and fail to reach the cell surface. The other three mutations specify precursors (100, 120, and 170 kd) that undergo a normal 40 kd increase in molecular weight and reach the surface, but do not bind LDL normally. Pedigree studies show that each mutation segregates as an allele at the LDL receptor locus. These data imply that signals for transport of receptors from endoplasmic reticulum to the cell surface are contained within the amino acid sequences of the receptors, and that mutations affecting these sequences can disrupt receptor transport.
低密度脂蛋白（LDL）受体最初合成时是一种120kd的前体，在前往细胞表面的过程中，其表观分子量会在翻译后增加40kd。我们描述了7个突变，这些突变会干扰77名临床诊断为纯合子家族性高胆固醇血症患者的成纤维细胞中受体的合成、加工和运输。一个突变消除了可免疫沉淀前体的合成。三个突变产生的前体（100kd、120kd和135kd）无法进行正常加工，也无法到达细胞表面。另外三个突变产生的前体（100kd、120kd和170kd）分子量正常增加40kd并到达细胞表面，但不能正常结合LDL。家系研究表明，每个突变都作为LDL受体位点的一个等位基因进行分离。这些数据表明，受体从内质网运输到细胞表面的信号包含在受体的氨基酸序列中，影响这些序列的突变会破坏受体运输。
