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-Structure paper
| タイトル | Structure and organization of AMPA receptor-TARP complexes in the mammalian cerebellum. |
|---|---|
| ジャーナル・号・ページ | Science, Page eaeb3577, Year 2025 |
| 掲載日 | 2025年12月11日 |
著者 | 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 / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:41379938 |
| 手法 | EM (単粒子) |
| 解像度 | 3.26 - 4.5 Å |
| 構造データ | EMDB-54543, PDB-9s3o: EMDB-54547, PDB-9s3q: EMDB-54556, PDB-9s3z: EMDB-54558, PDB-9s41: ![]() EMDB-54559: Cerebellar GluAx/A4 TMD with four TARPs (focused refinement) ![]() EMDB-55413: GluA4 N-terminal domain bound to nanobody NB74 (focused refinement) ![]() EMDB-55414: GluA4 LBD-TMD with TARP gamma 2 (focused refinement) ![]() EMDB-55418: GluA4 with TARP gamma2 (consensus refinement) ![]() EMDB-55419: Full-length GluA4 with TARP gamma 2 (composite map) |
| 化合物 | ![]() ChemComp-NAG: ![]() ChemComp-E2Q: |
| 由来 |
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キーワード | SIGNALING PROTEIN / AMPA ionotropic glutamate receptor |
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