Structure and organization of AMPA receptor-TARP complexes in the mammalian cerebellum

• 成果类型: Article
• 署名作者: Scrutton, Alexander M.; Sengupta, Nayanika; Ivica, Josip; Stockwell, Imogen; Peak-Chew, Sew; Singh, Bishal; Suzuki, Kunimichi; Chang, Veronica T.; McLaughlin, Stephen H.; Krieger, James M.; Aricescu, A. Radu; Greger, Ingo H.
• 署名单位: MRC Laboratory Molecular Biology; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); MRC Laboratory Molecular Biology; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); University of Texas System; UTMD Anderson Cancer Center; Keio University; MRC Laboratory Molecular Biology; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aeb3577
• 发表日期: 2026-03-26
• 关键词: glutamate receptors; terminal domain; subunit; expression; proteins; GAMMA-7; synapse; FAMILY; MODEL; mouse

摘要

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 posttranscriptional modifications. Using mass spectrometry, cryo-electron microscopy, and electrophysiology, we characterize major cerebellar AMPARs in pigs: calcium-impermeable GluA2/A4 heteromers with four transmembrane AMPAR regulatory protein (TARP) subunits, mainly neuronal in origin, and BG-specific, calcium-permeable GluA1/A4 heteromers containing two type II TARPs. We also showed that GluA4 receptors frequently 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.