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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Authors: | Xiao-Qian Fang Jindong Xu Shuang Feng Bradley R Groveman Shuang-Xiu Lin Xian-Min Yu |
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Institution: | (1) Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL 32306-4300, USA;(2) Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, Canada;(3) Department of Otolaryngology-Head and Neck Surgery, Guangxi Medical University, 530021 Nanning, People’s Republic of China; |
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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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