Jayaraman NMDA research published in Nature Communications
Recent research from the lab of Vasanthi Jayaraman, PhD, professor and John S. Dunn Chair in Biochemistry and Microbiology, studying the role that N-methyl-D-aspartate (NMDA) receptors play in converting chemical signals in the brain to electric ones, has been published in Nature Communications.
The paper titled “Bi-directional allosteric pathway in NMDA receptor activation and modulation” focuses on NMDA receptors, which play a key role in processes such as learning and memory, as well as in serious conditions like Alzheimer’s disease, Parkinson’s disease, epilepsy, and stroke.
NMDA receptors are made up primarily of GluN1 and GluN2 subunits, with the latter determining how the receptors behave in terms of how much they activate or shut down, with the extremes being represented by GluN2a and GluN2D subunits.
“Our study used a highly sensitive method called single-molecule fluorescence resonance energy transfer (smFRET) to observe how the receptor’s different parts move and communicate with each other,” Jayaraman said. “We focused on how the outside part (the amino-terminal domain) and the inner part (the transmembrane domain) of the receptor work together.”
Through their research, the lab discovered that when one part of the receptor changes, it directly affects other parts, showing a bidirectional communication between the regions.
“This dynamic interplay is key to how the receptor functions, and we found that the GluN2D subunit, in particular, has unique, highly flexible states that haven’t been seen before in structural studies,” Jayaraman said.
“These insights are not only important for understanding how these receptors work but could also inform future drug development,” Jayaraman said. “By targeting the receptor’s dynamic states, new treatments could be developed for neurological disorders linked to NMDA receptor function.”
The paper was co-written by Paula Bender, PhD candidate; Subhajit Chakraborty, PhD; Ryan J. Durham PhD; Vladimir Berka, PhD; and Elisa Carillo, PhD.