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The NMDA Receptor NR1 Subunit is Critically Involved in the Regulation of NMDA Receptor Activity by C-terminal Src kinase (Csk)

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Abstract

Previous studies have shown that Csk plays critical roles in the regulation of neural development, differentiation and glutamate-mediated synaptic plasticity. It has been found that Csk associates with the NR2A and 2B subunits of N-methyl-D-aspartate receptors (NMDARs) in a Src activity-dependent manner and serves as an intrinsic mechanism to provide a “brake” on the induction of long-term synaptic potentiation (LTP) mediated by NMDARs. In contrast to the NR2A and 2B subunits, no apparent tyrosine phosphorylation is found in the NR1 subunit of NMDARs. Here, we report that Csk can also associate with the NR1 subunit in a Src activity-dependent manner. The truncation of the NR1 subunit C-tail which contains only one tyrosine (Y837) significantly reduced the Csk association with the NR1-1a/NR2A receptor complex. Furthermore, we found that either the truncation of NR2A C-tail at aa 857 or the mutation of Y837 in the NR1-1a subunit to phenylalanine blocked the inhibition of NR1-1a/NR2A receptors induced by intracellular application of Csk. Thus, both the NR1 and NR2 subunits are required for the regulation of NMDAR activity by Csk.

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Acknowledgments

This work was supported by a grant from NIH (5R01 NS053567-04) to XMY. SF is supported by the State Scholarship Fund of China (2009845013). We also thank Dr. J. Olcese for his technical help.

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Authors and Affiliations

  1. Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL, 32306-4300, USA

    Xiao-Qian Fang, Shuang Feng, Bradley R. Groveman, Shuang-Xiu Lin & Xian-Min Yu

  2. Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, Canada

    Jindong Xu & Xian-Min Yu

  3. Department of Otolaryngology-Head and Neck Surgery, Guangxi Medical University, 530021, Nanning, People’s Republic of China

    Shuang Feng

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  1. Xiao-Qian Fang
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  2. Jindong Xu
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  5. Shuang-Xiu Lin
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Correspondence to Xian-Min Yu.

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Xiao-Qian Fang and Jindong Xu contributed to this work equally.

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Fang, XQ., Xu, J., Feng, S. et al. The NMDA Receptor NR1 Subunit is Critically Involved in the Regulation of NMDA Receptor Activity by C-terminal Src kinase (Csk). Neurochem Res 36, 319–326 (2011). https://doi.org/10.1007/s11064-010-0330-0

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  • DOI: https://doi.org/10.1007/s11064-010-0330-0

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