9s3o | pdb_00009s3o
Cerebellar GluA2/4 NTD heterophilic tetramer interface (focused refinement)
Structural highlights
FunctionI3L8N9_PIG Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system and plays an important role in fast excitatory synaptic transmission. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate.[ARBA:ARBA00058337] Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system.[RuleBase:RU367118] Publication Abstract from PubMedAMPA 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. Structure and organization of AMPA receptor-TARP complexes in the mammalian cerebellum.,Scrutton AM, Sengupta N, Ivica J, Stockwell I, Peak-Chew S, Singh B, Suzuki K, Chang VT, McLaughlin SH, Krieger JM, Aricescu AR, Greger IH Science. 2025 Dec 11:eaeb3577. doi: 10.1126/science.aeb3577. PMID:41379938[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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