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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00334

The C-terminus of NMDAR GluN1-1a Subunit Translocates to Nucleus and Regulates Synaptic Function

 LIANG ZHOU1* and Jingjing Duan2, 3
  • 1Soochow University, China
  • 2Sun Yat-sen University, China
  • 3Zhongshan School of Medicine, Sun Yat-sen University, China

NMDARs, the Ca2+ permeable channels, play central roles in synaptic plasticity, brain development, learning and memory. NMDAR binding partners and associated signaling has been extensively studied in synapse-to-nucleus communications. However, whether NMDARs could directly regulate synapse-to-nucleus communications is largely unknown. Here, we analyze the four alternative splicing of the C-terminus isoforms of GluN1 (1a, 2a, 3a, and 4a), and find that C1 domain of GluN1 is necessary for nuclear localization. Besides, we find that the 10 basic amino acids in C1 domain determine the nuclear localization of GluN1 C-terminus. Further investigating the expression patterns of the full length of GluN1 four isoforms shows that only GluN-1a exhibits the cytoplasmic and nucleus distribution in primary hippocampal neurons. Electrophysiological analyses also show that over-expression of GluN1 C-terminus without C1 domain doesn't affect synaptic transmission, whereas GluN1 C-terminus containing C1 domain potentiates NMDAR-mediated synaptic transmission. Our data suggested that the 10 basic amino acids in C1 domain determine translocation of GluN1 C-terminus into nucleus and regulate synaptic transmission.

Keywords: NMDA receptor, synapse-to-nucleus communication, GluN1, Synapse Transmission, cLTP

Received: 20 Jun 2018; Accepted: 12 Sep 2018.

Edited by:

Mario E. GUIDO, Center for Research in Biological Chemistry Córdoba (CIQUIBIC), Argentina

Reviewed by:

John J. Woodward, Medical University of South Carolina, United States
Marina Mikhaylova, Universitätsklinikum Hamburg-Eppendorf, Germany  

Copyright: © 2018 ZHOU and Duan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. LIANG ZHOU, Soochow University, Suzhou, China, liangzhou@suda.edu.cn