Scientists have long understood the crucial role of protons in synaptic signaling, but a new study has shed light on their specific mechanism of action. Researchers from the labs of Teru Nakagawa and Ingo Greger discovered that a brief decrease in pH can lead to changes in the structure of AMPA receptors (AMPARs), thereby modulating their location and gating kinetics.
During synaptic transmission, protons are released together with glutamate, and these co-released protons participate in synaptic signaling mediated by AMPARs. The study found that when protons interact with a specific amino acid in an AMPAR, they cause the receptor’s N-terminal domain to splay in half. This change has two key effects: it slows the receptor’s recovery before it can activate again and increases receptor diffusion by breaking its anchor from the optimal location for activation.
This discovery has significant implications for our understanding of short-term and long-term synaptic plasticity, as well as the molecular processes behind cognition, learning, and memory formation. Deficiencies in AMPAR functioning have been linked to various neurological and psychiatric disorders, including seizures, Alzheimer’s disease, major depressive disorder, limbic encephalitis, intellectual disability, and autism spectrum disorder.
The study, published in Nature Structural & Molecular Biology, provides new insights into the role of protons in synaptic transmission and has potential implications for our understanding of brain injury and recovery.
Source: https://phys.org/news/2024-08-protons-tune-synaptic-protein-receptor.html