一种需要组成型和上下文相关锚定 AMPA 受体的诺琳组织的细胞外蛋白质网络。
A Noelin-organized extracellular network of proteins required for constitutive and context-dependent anchoring of AMPA-receptors.
机构信息
Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany.
National Eye Institute, Section of Retinal Ganglion Cell Biology, National Institutes of Health, Bethesda, MD, USA.
出版信息
Neuron. 2023 Aug 16;111(16):2544-2556.e9. doi: 10.1016/j.neuron.2023.07.013.
Information processing and storage in the brain rely on AMPA-receptors (AMPARs) and their context-dependent dynamics in synapses and extra-synaptic sites. We found that distribution and dynamics of AMPARs in the plasma membrane are controlled by Noelins, a three-member family of conserved secreted proteins expressed throughout the brain in a cell-type-specific manner. Noelin tetramers tightly assemble with the extracellular domains of AMPARs and interconnect them in a network-like configuration with a variety of secreted and membrane-anchored proteins including Neurexin1, Neuritin1, and Seizure 6-like. Knock out of Noelins1-3 profoundly reduced AMPARs in synapses onto excitatory and inhibitory (inter)neurons, decreased their density and clustering in dendrites, and abolished activity-dependent synaptic plasticity. Our results uncover an endogenous mechanism for extracellular anchoring of AMPARs and establish Noelin-organized networks as versatile determinants of constitutive and context-dependent neurotransmission.
大脑中的信息处理和存储依赖于 AMPA 受体 (AMPARs) 及其在突触和突触外部位的依赖于上下文的动力学。我们发现，质膜中 AMPAR 的分布和动力学受 Noelin 控制，Noelin 是一个由三个成员组成的保守分泌蛋白家族，在大脑中以细胞类型特异性的方式表达。Noelin 四聚体与 AMPAR 的细胞外结构域紧密组装，并将它们与各种分泌和膜锚定蛋白（包括 Neurexin1、Neuritin1 和 Seizure 6-like）相互连接成网络状结构。Noelin1-3 的敲除显著减少了兴奋性和抑制性（间）神经元上突触中的 AMPAR，减少了树突中 AMPAR 的密度和聚集，并消除了活性依赖性突触可塑性。我们的研究结果揭示了 AMPAR 细胞外锚定的内源性机制，并确立了 Noelin 组织的网络作为组成型和依赖于上下文的神经传递的多功能决定因素。
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