Super-resolution imaging reveals the nanoscale organization of metabotropic glutamate receptors at presynaptic active zones
Super-resolution imaging reveals the nanoscale organization of metabotropic glutamate receptors at presynaptic active zones
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DOI：
10.1126/sciadv.aay7193
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发表时间：
2020-04
期刊：
影响因子：
13.6
通讯作者：
Sana Siddig;S. Aufmkolk;S. Doose;Marie-Lise Jobin;Christian Werner;M. Sauer;D. Calebiro
中科院分区：
文献类型：
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作者：
Sana Siddig;S. Aufmkolk;S. Doose;Marie-Lise Jobin;Christian Werner;M. Sauer;D. Calebiro
超分辨率成像揭示了mGluR 4，CaV2.1和Munc-18-1在小脑活动区之间的密切联系。G蛋白偶联受体（GPCRs）在突触传递的调节中起着重要作用。代谢型谷氨酸受体4（mGluR 4）提供了一个关键的例子，它抑制突触前活动区（AZ）的谷氨酸释放。然而，GPCR如何在AZ内组织以调节神经传递仍然在很大程度上未知。在这里，我们应用双色超分辨率成像的直接随机光学重建显微镜（dSTORM），以探讨在小鼠小脑的平行纤维AZ的mGluR 4的纳米级组织。我们发现一个不均匀的分布，与多个纳米结构域内AZ，每个含有，平均而言，一到两个mGluR 4亚基。在这些纳米结构域中，mGluR 4通常位于电压依赖性CaV2.1通道和Munc-18-1附近，这两者对于神经递质释放都是必不可少的。这些发现提供了以前未知的见解GPCR在AZ的分子组织，这表明mGluR 4和调节突触传递的分泌机制之间的密切联系可能的含义。
Super-resolution imaging reveals close association between mGluR4, CaV2.1, and Munc-18-1 at cerebellar active zones. G protein–coupled receptors (GPCRs) play a fundamental role in the modulation of synaptic transmission. A pivotal example is provided by the metabotropic glutamate receptor type 4 (mGluR4), which inhibits glutamate release at presynaptic active zones (AZs). However, how GPCRs are organized within AZs to regulate neurotransmission remains largely unknown. Here, we applied two-color super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) to investigate the nanoscale organization of mGluR4 at parallel fiber AZs in the mouse cerebellum. We find an inhomogeneous distribution, with multiple nanodomains inside AZs, each containing, on average, one to two mGluR4 subunits. Within these nanodomains, mGluR4s are often localized in close proximity to voltage-dependent CaV2.1 channels and Munc-18-1, which are both essential for neurotransmitter release. These findings provide previously unknown insights into the molecular organization of GPCRs at AZs, suggesting a likely implication of a close association between mGluR4 and the secretory machinery in modulating synaptic transmission.