Yang Tao, Williams Bart O
Program in Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan.
Physiol Rev. 2017 Jul 1;97(3):1211-1228. doi: 10.1152/physrev.00013.2016.
The identification of the low-density lipoprotein receptor (LDLR) provided a foundation for subsequent studies in lipoprotein metabolism, receptor-mediated endocytosis, and many other fundamental biological functions. The importance of the LDLR led to numerous studies that identified homologous molecules and ultimately resulted in the description of the LDL-receptor superfamily, a group of proteins that contain domains also found in the LDLR. Subsequent studies have revealed that members of the LDLR-related protein family play roles in regulating many aspects of signal transduction. This review is focused on the roles of selected members of this protein family in skeletal development and disease. We present background on the identification of this subgroup of receptors, discuss the phenotypes associated with alterations in their function in human patients and mouse models, and describe the current efforts to therapeutically target these proteins to treat human skeletal disease.
低密度脂蛋白受体（LDLR）的鉴定为后续脂蛋白代谢、受体介导的内吞作用以及许多其他基本生物学功能的研究奠定了基础。LDLR的重要性引发了众多研究，这些研究鉴定出了同源分子，并最终促成了LDL受体超家族的描述，这是一组包含在LDLR中也能找到的结构域的蛋白质。随后的研究表明，LDLR相关蛋白家族的成员在调节信号转导的许多方面发挥作用。本综述聚焦于该蛋白家族特定成员在骨骼发育和疾病中的作用。我们介绍了该受体亚组鉴定的背景，讨论了人类患者和小鼠模型中其功能改变相关的表型，并描述了目前针对这些蛋白质进行治疗以治疗人类骨骼疾病的努力。
