N-glycan content modulates kainate receptor functional properties.
N-glycan content modulates kainate receptor functional properties.
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N-聚糖含量调节红藻氨酸受体功能特性。
DOI：
10.1113/jp274790
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Swanson,GeoffreyT
中科院分区：
文献类型：
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作者：
Vernon,ClaireG;Copits,BryanA;Stolz,JacobR;Guzmán,YomayraF;Swanson,GeoffreyT
关键点离子型谷氨酸受体（iGluR）亚基在4-12个位点被N-糖基化，高尔基体加工产生含有高甘露糖、杂合和复杂寡糖的成熟受体。N-糖基化对受体生物发生至关重要，影响受体运输，并为碳水化合物结合蛋白提供结合位点。聚糖部分大，极性，偶尔带电荷，它们附着在沿着iGluR的位点上，这些位点使它们参与门控的结构变化。改变红藻氨酸受体（KAR）（iGluR的一个亚家族）上的聚糖含量，改变受体的功能特性，例如脱敏，从脱敏和失活中恢复。我们报告了第一个观察结果，即带电三糖HNK-1与天然KAR缀合，我们发现它显著改变了重组KAR的功能特性。我们的结果表明，N-聚糖的分子组成可以影响KAR的生物物理特性，离子型谷氨酸受体（iGluRs）是一种四聚体蛋白，每个亚基上有4 - 12个N-糖基化位点，这可能使其具有高度的结构多样性。N-糖基化是哺乳动物细胞中iGluRs正确折叠所必需的，尽管寡糖对成功折叠的受体功能的影响尚不清楚。聚糖部分是大的、极性的、偶尔带电荷的，并且在整个神经系统中介导许多蛋白质-蛋白质相互作用。此外，它们附着在沿着iGluR亚基的位点，这些亚基定位它们以参与门控的结构变化。在本研究中，我们表明，改变红藻氨酸受体（KARs）上的聚糖含量改变受体的功能特性的方式依赖于身份的修饰的糖和亚基组成的受体，它们所连接的。我们还报告了天然KAR携带复杂的加帽寡糖人类自然杀伤细胞-1。糖基化模式可能在细胞类型之间、在发育过程中或在病理状态下不同，因此我们的研究结果揭示了通过聚糖结构的多样性对KAR功能进行背景特异性微调的潜在机制。
Key pointsIonotropic glutamate receptor (iGluR) subunits areN‐glycosylated at 4–12 sites, and Golgi processing produces mature receptors that contain high‐mannose, hybrid and complex oligosaccharides.N‐glycosylation is crucial for receptor biogenesis, influences receptor trafficking and provides a binding site for carbohydrate binding proteins.Glycan moieties are large, polar and occasionally charged, and they are attached at sites along iGluRs that position them for involvement in the structural changes underlying gating.Altering glycan content on kainate receptors (KARs), a subfamily of iGluRs, changes functional properties of the receptor, such as desensitization, recovery from desensitization and deactivation.We report the first observation that the charged trisaccharide HNK‐1 is conjugated to native KARs, and we find that it substantially alters recombinant KAR functional properties.Our results show that the molecular composition ofN‐glycans can influence KAR biophysical properties, revealing a potential mechanism for fine‐tuning the function of these receptors.AbstractIonotropic glutamate receptors (iGluRs) are tetrameric proteins with between four and 12 consensus sites forN‐glycosylation on each subunit, which potentially allows for a high degree of structural diversity conferred by this post‐translational modification.N‐glycosylation is required for proper folding of iGluRs in mammalian cells, although the impact of oligosaccharides on the function of successfully folded receptors is less clear. Glycan moieties are large, polar, occasionally charged and mediate many protein–protein interactions throughout the nervous system. Additionally, they are attached at sites along iGluR subunits that position them for involvement in the structural changes underlying gating. In the present study, we show that altering glycan content on kainate receptors (KARs) changes the functional properties of the receptors in a manner dependent on the identity of both the modified sugars and the subunit composition of the receptor to which they are attached. We also report that native KARs carry the complex capping oligosaccharide human natural killer‐1. Glycosylation patterns probably differ between cell types, across development or with pathologies, and thus our findings reveal a potential mechanism for context‐specific fine‐tuning of KAR function through diversity in glycan structure.