近日，MRC分子生物学实验室
通过质谱、低温电镜和电生理学，研究人员对猪小脑AMPARs的主要特征进行了表征：钙不渗透性GluA2/A4异构体及其TARP亚基，主要来自神经元，以及含有两种2型TARP的BG特异性钙渗透性GluA1/A4异构体。课题组研究人员还发现，GluA4受体始终表现出紧凑的n端结构域，促进其突触传递。他们的研究定义了哺乳动物小脑AMPAR复合物的组织原理，并揭示了不同受体亚型如何支持细胞类型特异性功能。
据了解，AMPA受体（AMPARs）是谷氨酸能信号在整个大脑中的多模态转导器。它们的多样性在小脑中得到体现；在传入突触，AMPARs介导高频兴奋，而在伯格曼胶质细胞（BG）中，它们支持钙瞬态，从而调节突触传递。这一光谱源于核心亚基（GluA1-4）、辅助蛋白和转录后修饰的不同组合。
附：英文原文
Title: Structure and organization of AMPA receptor-TARP complexes in the mammalian cerebellum
Author: Alexander M. Scrutton, Nayanika Sengupta, Josip Ivica, Imogen Stockwell, Sew Peak-Chew, Bishal Singh, Kunimichi Suzuki, Veronica T. Chang, Stephen H. McLaughlin, James M. Krieger, A. Radu Aricescu, Ingo H. Greger
Issue&Volume: 2025-12-11
Abstract: AMPA receptors (AMPARs) are multimodal transducers of glutamatergic signals throughout the brain. Their diversity is exemplified in the cerebellum; at afferent synapses, AMPARs mediate high-frequency excitation, whereas in Bergmann glia (BG) they support calcium transients that modulate synaptic transmission. This spectrum arises from different combinations of core subunits (GluA1-4), auxiliary proteins, and post-transcriptional modifications. Here, using mass-spectrometry, cryo-EM, and electrophysiology, we characterize major cerebellar AMPARs in pig: calcium-impermeable GluA2/A4 heteromers with four TARP subunits, mainly neuronal in origin, and BG-specific calcium-permeable GluA1/A4 heteromers containing two Type-2 TARPs. We also showed that GluA4 receptors consistently exhibit compact N-terminal domains that promote their synaptic delivery. Our study defines the organizational principles of mammalian cerebellar AMPAR complexes and reveals how different receptor subtypes support cell-type specific functions.
DOI: aeb3577
Source: https://www.science.org/doi/10.1126/science.aeb3577