Science Topics – 175
AMPA receptor is a protein responsible for excitatory synaptic transmission in the brain. It has been believed that AMPA receptors assemble at the postsynaptic density, thereby increasing the efficiency of neurotransmission. However, the mechanism how AMPA receptors assemble was not fully understood. In this study, we used high-speed atomic force microscopy to observe how the extracellular domains of AMPA receptors move (left panel). It was revealed that the dimers of the extracellular domains, which were previously thought to be solid, not only widely fluctuate but also split (middle panel) and associate together repeatedly. Furthermore, it was also observed that the split dimer binds to the other dimer in neighboring AMPA receptors (right panel), which clearly indicates that “dimer exchange” is a plausible candidate of the mechanism that promotes the assembly of AMPA receptors at synapses.
AMPA receptors are molecules related to epileptic seizures, and drugs that inhibit their operation are considered as an important treatment. Therefore, this study are expected not only to provide new insights into the molecular mechanisms of excitatory neurotransmission, but also to contribute to the creation of innovative therapeutic agents for related diseases.
Sumino A, Sumikama T, Zhao Y, Flechsig H, Umeda K, Kodera N, Konno H, Hattori M, Shibata M. High-Speed Atomic Force Microscopy Reveals Fluctuations and Dimer Splitting of the N-Terminal Domain of GluA2 Ionotropic Glutamate Receptor-Auxiliary Subunit Complex. ACS Nano : ppp-ppp, 2024.
＜Figure Legends＞
Molecular dynamics of the extracellular domains of the AMPA receptors observed by high-speed atomic force microscopy (top) and schematic diagram (bottom).
1Nano Life Science Institute, Kanazawa University, Japan
2Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, China