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首页> 外文期刊>Journal of Molecular Biology >Hidden Twins: SorCS Neuroreceptors Form Stable Dimers
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Hidden Twins: SorCS Neuroreceptors Form Stable Dimers

机译：隐藏的双胞胎：索氏神经感受器形成稳定的二聚体

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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.
机译：Sorcs1，Sorcs2和Sorcs3属于VPS10P-Domain of Mulliligand受体。遗传和功能性研究将Sorcs受体与精神疾病，阿尔茨海默病和2型糖尿病有联系，展示了神经元功能和代谢控制的关键作用。令人惊讶的是，到目前为止，他们的结构组成尚未研究。在这里，我们使用生物化学方法和电子显微镜具有索引1，Sorcs2和Sorcs3。我们发现它们纯化的细胞外结构域共存在稳定的二聚体和单体群中。这是通过共免疫沉淀实验支持的，其中膜结合二聚体从细胞裂解物中成功拉出。虽然二聚体几乎不可用，但通过酶促脱糖基化促进单体群的二聚化。我们得出结论，翻译后修饰，特别是糖基化的程度和模式，调节蛋白质的低聚状态。因此，细胞可以通过控制单体和二聚体之间的比例来规定配体特异性，因此调节索氏受体的多种功能。 （c）2017 Elsevier Ltd.保留所有权利。

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