Molecular characterization of the first avian LDL receptor: role in sterol metabolism of ovarian follicular cells
Molecular characterization of the first avian LDL receptor: role in sterol metabolism of ovarian follicular cells
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DOI：
10.1194/jlr.m300014-jlr200
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发表时间：
2003-09-01
影响因子：
6.5
通讯作者：
Schneider, WJ
中科院分区：
文献类型：
--
作者：
Hummel, S;Lynn, EG;Schneider, WJ
低表达水平和缓慢的甾醇介导的调节可能是迄今为止未能对产卵物种中真正的 LDL 受体 (LDLR) 进行分子表征的原因。此处通过 cDNA 克隆描述的鸡 LDLR 的整体结构在进化中得到了保守，因为哺乳动物 LDLR 的标志特性已经存在于禽类蛋白质中。鸡受体似乎更喜欢 LDL 而不是 VLDL 作为配体，这符合其为卵巢滤泡细胞中类固醇生成提供脂蛋白衍生胆固醇的主要作用。这也与以下事实相一致：尽管显着刺激了 VLDL 的产生，但雌激素的施用增加了公鸡肝脏 LDLR 的表达。在培养的鸡胚成纤维细胞中，通过与胆固醇合成抑制剂（例如他汀类药物）一起孵育来诱导受体的表达。此外，用特异性抗受体抗体预孵育诱导细胞可阻断 LDL 内吞作用，证明受体具有配体内吞作用。最后，LDLR 在卵细胞外细胞群中的分布为卵泡内雌激素产生的三细胞模型提供了支持。总之，第一个禽类 LDLR 的分子表征揭示了 LDLR 相关蛋白超基因家族成员的进化、结构和功能方面的新信息。
Low levels of expression and sluggish sterol-mediated regulation have been likely reasons for the failure to molecularly characterize a bona fide LDL receptor (LDLR) in egg-laying species to date. The overall structure of the chicken LDLR, delineated here by cDNA cloning, has been conserved in evolution, since hallmark properties of mammalian LDLRs are already present in the avian protein. The chicken receptor appears to prefer LDL over VLDL as ligand, in compliance with its main role in providing lipoprotein-derived cholesterol for steroid production in ovarian follicular cells. This is also compatible with the fact that estrogen administration increased hepatic LDLR expression in roosters despite dramatically stimulated VLDL production. In cultured chicken embryo fibroblasts, expression of the receptor was induced by incubation with cholesterol synthesis inhibitors such as a statin. Furthermore, preincubation of induced cells with a specific anti-receptor antibody blocks LDL endocytosis, demonstrating that the receptor is ligand-endocytosis competent. Finally, the distribution of LDLRs among the extraoocytic cell populations lends support to a three-cell model for estrogen production within the ovarian follicle. In summary, the molecular characterization of the first avian LDLR reveals novel information about evolutionary, structural, and functional aspects of members of the supergene family of LDLR-related proteins.