Assembly and gating mechanism of native AMPA receptors from the cerebellum - PubMed
3 hours ago
- #AMPA receptors
- #Synaptic transmission
- #Cerebellum
- AMPA receptors (AMPARs) mediate fast excitatory synaptic transmission in the central nervous system.
- Calcium-permeable AMPARs and GluA4-containing receptors are crucial for cerebellar functions like motor learning and synaptic plasticity.
- Cerebellar AMPARs have a higher proportion of GluA4 compared to hippocampal and cortical AMPARs, which are predominantly GluA2-containing.
- A highly GluA4-specific antibody was generated to study native AMPARs in the cerebellum.
- Subunit compositions of both calcium-impermeable and calcium-permeable native AMPARs in the cerebellum were determined.
- GluA1 and GluA4-containing cerebellar AMPARs are calcium-permeable, with GluA4 mainly in B/D positions and GluA1 in A/C positions, associated with cornichon 3 (CNIH3).
- Structures of the AMPAR complex in resting, active, and desensitized states were determined, revealing conformational transitions.
- During desensitization, the receptor adopts a pseudo-4-fold configuration in the ligand-binding domain layer.
- The study provides insights into AMPAR-mediated synaptic transmission in the cerebellum.