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bioRxiv · 10.1101/2020.08.21.261388

Contributions by N-terminal Domains to NMDA Receptor Currents

Amico-Ruvio, S. A.·Paganelli, M. A.·Abbott, J. A.·Myers, J. M.·Kasperek, E. M.·Iacobucci, G. J.·Popescu, G. K.
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Abstract

To investigate the role of the N-terminal domains (NTDs) in NMDA receptor signaling we used kinetic analyses of one-channel currents and compared the reaction mechanism of recombinant wild-type GluN1/GluN2A and GluN1/GluN2B receptors with those observed for NDT-lacking receptors. We found that truncated receptors maintained the fundamental gating mechanism characteristic of NMDA receptors, which includes a multi-state activation sequence, desensitization steps, and mode transitions. This result establishes that none of the functionally-defined NMDA receptor activation events require the NTD. Notably, receptors that lacked the entire NTD layer retained isoform-specific kinetics. Together with previous reports, these results demonstrate that the entire gating machinery of NMDA receptors resides within a core domain that contains the ligand-binding and the channel-forming transmembrane domains, whereas the NTD and C-terminal layers serve modulatory functions, exclusively.

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Amico-Ruvio, S. A., Paganelli, M. A., Abbott, J. A., Myers, J. M., Kasperek, E. M., Iacobucci, G. J., Popescu, G. K.. 2020-08-23. Contributions by N-terminal Domains to NMDA Receptor Currents. https://doi.org/10.1101/2020.08.21.261388

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