Lipoprotein receptors--an evolutionarily ancient multifunctional receptor family.
Lipoprotein receptors--an evolutionarily ancient multifunctional receptor family.
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DOI：
10.1515/bc.2010.129
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发表时间：
2010-11
影响因子：
3.7
通讯作者：
Herz J
中科院分区：
文献类型：
--
作者：
Dieckmann M;Dietrich MF;Herz J
脂蛋白受体是进化上古老的蛋白质，表达在许多细胞类型的表面。从第一个原始多细胞生物体的出现开始，进化出了几个结构和功能不同的脂蛋白受体家族。最初，这些细胞表面蛋白被认为只是调节细胞之间的脂类和营养物质的运输，在某些情况下，通过充当清道夫受体，从细胞外空间和细胞表面清除其他类型的大分子，如蛋白酶和蛋白水解酶抑制剂。在过去的十年里，这一图景大大扩大了。我们现在意识到，这些受体中的许多不仅仅是货物运输器；它们深深地嵌入了细胞之间相互交流的机制中。通过与基本信号通路的物理相互作用和共同进化，脂蛋白受体占据了基本的和令人惊讶的多样化的功能，这些功能对于整合发育过程中和分化组织中复杂的细胞信号输入网络是必不可少的。此外，脂蛋白受体调节淀粉样前体蛋白(APP)和β-淀粉样多肽(Aβ)的细胞转运和定位，提示在阿尔茨海默病的发病机制中发挥了作用。此外，令人信服的证据表明，低密度脂蛋白受体家族成员参与了肿瘤的发生和发展。
Lipoprotein receptors are evolutionarily ancient proteins that are expressed on the surface of many cell types. Beginning with the appearance of the first primitive multicellular organisms several structurally and functionally distinct families of lipoprotein receptors evolved. Originally, these cell surface proteins were thought to merely mediate the traffic of lipids and nutrients between cells and in some cases, by functioning as scavenger receptors, remove other kinds of macromolecules, such as proteases and protease inhibitors from the extracellular space and the cell surface. Over the last decade, this picture has greatly expanded. We now appreciate that many of these receptors are not mere cargo transporters; they are deeply embedded in the machinery by which cells communicate with each other. By physically interacting and coevolving with fundamental signaling pathways, lipoprotein receptors have occupied essential and surprisingly diverse functions that are indispensable for integrating the complex web of cellular signal input during development and in differentiated tissues. Furthermore, lipoprotein receptors modulate cellular trafficking and localization of the amyloid precursor protein (APP) and the β-amyloid peptide (Aβ), suggesting a role in the pathogenesis of Alzheimer’s disease. Moreover, compelling evidence shows that low density lipoprotein receptor family members are involved in tumor development and progression.