Hidden Twins: SorCS Neuroreceptors Form Stable Dimers
Hidden Twins: SorCS Neuroreceptors Form Stable Dimers
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DOI：
10.1016/j.jmb.2017.08.006
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发表时间：
2017-09-15
影响因子：
5.6
通讯作者：
Moeller, Arne
中科院分区：
文献类型：
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作者：
Januliene, Dovile;Manavalan, Arulmani;Moeller, Arne
SorCS 1、SorCS 2和SorCS 3属于多配体受体的Vps 10 p-结构域家族。遗传和功能研究已经将SorCS受体与精神疾病、阿尔茨海默病和2型糖尿病联系起来，证明了其在神经元功能和代谢控制中的关键作用。令人惊讶的是，它们的结构组成迄今尚未被研究。在这里，我们的特点SorCS 1，SorCS 2和SorCS 3使用生化方法和电子显微镜。我们发现，他们的纯化的胞外结构域共存于稳定的二聚体和单体群体。这得到了免疫共沉淀实验的支持，其中膜结合二聚体被成功地从细胞裂解物中拉下来。虽然二聚体实际上是牢不可破的，但通过酶促去糖基化促进了单体群体的二聚化。我们的结论是翻译后修饰，特别是糖基化的程度和模式，调节蛋白质的寡聚状态。因此，细胞可以通过控制单体和二聚体之间的比例来决定配体特异性，从而调节SorCS受体的多种功能。(C)2017爱思唯尔有限公司版权所有
SorCS1, SorCS2 and SorCS3 belong to the Vps10p-domain family of multiligand receptors. Genetic and functional studies have linked SorCS receptors to psychiatric disorders, Alzheimer's disease and type 2 diabetes, demonstrating critical roles in neuronal functionality and metabolic control. Surprisingly, their structural composition has so far not been studied. Here we have characterized SorCS1, SorCS2 and SorCS3 using biochemical methods and electron microscopy. We found that their purified extracellular domains co-exist in stable dimeric and monomeric populations. This was supported by co-immunoprecipitation experiments, where membrane-bound dimers were successfully pulled down from cell lysate. While dimers were virtually unbreakable, dimerization of the monomeric population was promoted through enzymatic deglycosylation. We conclude that post-translational modifications, specifically the degree and pattern of glycosylation, regulate the oligomeric state of the protein. Hence, cells may dictate ligand specificity by controlling the ratio between monomers and dimers and, therefore, regulate the multiple functions of SorCS receptors. (C) 2017 Elsevier Ltd. All rights reserved.