About this Biochemistry, Genetics and Molecular Biology article
α2δ-1 switches the phenotype of synaptic AMPA receptors by physically disrupting heteromeric subunit assembly by Lingyong Li; Shao-Rui Chen; Meng-Hua Zhou; Li Wang; De-Pei Li; Hong Chen; Garam Lee; Vasanthi Jayaraman; Hui-Lin Pan is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
## SUMMARY Many neurological disorders show an increased prevalence of GluA2-lacking, Ca^2+^-permeable AMPA receptors (CP-AMPARs), which dramatically alters synaptic function. However, the molecular mechanism underlying this distinct synaptic plasticity remains enigmatic. Here, we show that nerve injury potentiates postsynaptic, but not presynaptic, CP-AMPARs in the spinal dorsal horn via α2δ-1. Overexpressing α2δ-1, previously regarded as a Ca^2+^ channel subunit, augments CP-AMPAR levels at the cell surface and synapse. Mechanistically, α2δ-1 physically interacts with both GluA1 and GluA2 via its C terminus, inhibits the GluA1/GluA2 heteromeric assembly, and increases GluA2 retention in the endoplasmic reticulum. Consequently, α2δ-1 diminishes the availability and synaptic expression of GluA1/GluA2 heterotetramers in the spinal cord in neuropathic pain. Inhibiting α2δ-1 with gabapentin or disrupting the α2δ-1-AMPAR complex fully restores the intracellular assembly and synaptic dominance of heteromeric GluA1/GluA2 receptors. Thus, α2δ-1 is a pivotal AMPAR-interacting protein that controls the subunit composition and Ca^2+^ permeability of postsynaptic AMPARs.
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- Author
- Lingyong Li; Shao-Rui Chen; Meng-Hua Zhou; Li Wang; De-Pei Li; Hong Chen; Garam Lee; Vasanthi Jayaraman; Hui-Lin Pan
- Publisher
- Elsevier BV
- Published
- 2021
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)