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- W3096810954 abstract "Abstract Although numerous pathogenic mutations have been identified in various subunits of N -methyl-D-aspartate receptors (NMDARs), ionotropic glutamate receptors that are central to glutamatergic neurotransmission, the functional effects of these mutations are often unknown. Here, we combined in silico modelling with microscopy, biochemistry, and electrophysiology in cultured HEK293 cells and hippocampal neurons to examine how the pathogenic missense mutation S688Y in the GluN1 NMDAR subunit affects receptor function and trafficking. We found that the S688Y mutation significantly increases the EC 50 of both glycine and d -serine in GluN1/GluN2A and GluN1/GluN2B receptors, and significantly slows desensitisation of GluN1/GluN3A receptors. Moreover, the S688Y mutation reduces the surface expression of GluN3A-containing NMDARs in cultured hippocampal neurons, but does not affect the trafficking of GluN2-containing receptors. Finally, we found that the S688Y mutation reduces Ca 2+ influx through NMDARs and reduces NMDA-induced excitotoxicity in cultured hippocampal neurons. These findings provide key insights into the molecular mechanisms that underlie the regulation of NMDAR subtypes containing pathogenic mutations." @default.
- W3096810954 created "2020-11-09" @default.
- W3096810954 creator A5008739835 @default.
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- W3096810954 date "2020-10-29" @default.
- W3096810954 modified "2023-09-27" @default.
- W3096810954 title "The pathogenic S688Y mutation in the ligand-binding domain of the GluN1 subunit regulates the properties of NMDA receptors" @default.
- W3096810954 cites W1537179351 @default.
- W3096810954 cites W1857698276 @default.
- W3096810954 cites W1915631305 @default.
- W3096810954 cites W1922786159 @default.
- W3096810954 cites W1952831770 @default.
- W3096810954 cites W1966515122 @default.
- W3096810954 cites W1966556202 @default.
- W3096810954 cites W1968653223 @default.
- W3096810954 cites W1969451153 @default.
- W3096810954 cites W1978023994 @default.
- W3096810954 cites W1983419147 @default.
- W3096810954 cites W1996507132 @default.
- W3096810954 cites W1998895310 @default.
- W3096810954 cites W2005147790 @default.
- W3096810954 cites W2009674315 @default.
- W3096810954 cites W2013812562 @default.
- W3096810954 cites W2024380057 @default.
- W3096810954 cites W2027844417 @default.
- W3096810954 cites W2028133023 @default.
- W3096810954 cites W2033759150 @default.
- W3096810954 cites W2037852973 @default.
- W3096810954 cites W2039872800 @default.
- W3096810954 cites W2043830156 @default.
- W3096810954 cites W2044958998 @default.
- W3096810954 cites W2047283392 @default.
- W3096810954 cites W2048142982 @default.
- W3096810954 cites W2049902088 @default.
- W3096810954 cites W2053361108 @default.
- W3096810954 cites W2056470034 @default.
- W3096810954 cites W2062928716 @default.
- W3096810954 cites W2065430019 @default.
- W3096810954 cites W2073744310 @default.
- W3096810954 cites W2078729100 @default.
- W3096810954 cites W2084556785 @default.
- W3096810954 cites W2088307620 @default.
- W3096810954 cites W2091765514 @default.
- W3096810954 cites W2096489570 @default.
- W3096810954 cites W2096844175 @default.
- W3096810954 cites W2103535314 @default.
- W3096810954 cites W2113944645 @default.
- W3096810954 cites W2121446334 @default.
- W3096810954 cites W2124023477 @default.
- W3096810954 cites W2134967712 @default.
- W3096810954 cites W2135766569 @default.
- W3096810954 cites W2149492210 @default.
- W3096810954 cites W2158669781 @default.
- W3096810954 cites W2164740045 @default.
- W3096810954 cites W2166442349 @default.
- W3096810954 cites W2167313026 @default.
- W3096810954 cites W2169678694 @default.
- W3096810954 cites W2234053937 @default.
- W3096810954 cites W2260891265 @default.
- W3096810954 cites W2286381411 @default.
- W3096810954 cites W2345316450 @default.
- W3096810954 cites W2510475597 @default.
- W3096810954 cites W2519837467 @default.
- W3096810954 cites W2537817793 @default.
- W3096810954 cites W2549889200 @default.
- W3096810954 cites W2550618833 @default.
- W3096810954 cites W2574596077 @default.
- W3096810954 cites W2581539125 @default.
- W3096810954 cites W2582131368 @default.
- W3096810954 cites W2589239610 @default.
- W3096810954 cites W2604355298 @default.
- W3096810954 cites W2604971413 @default.
- W3096810954 cites W2624067177 @default.
- W3096810954 cites W2736433134 @default.
- W3096810954 cites W2765949949 @default.
- W3096810954 cites W2788828922 @default.
- W3096810954 cites W2796358872 @default.
- W3096810954 cites W2804386291 @default.
- W3096810954 cites W2888998143 @default.
- W3096810954 cites W2891947782 @default.
- W3096810954 cites W2900149431 @default.
- W3096810954 cites W2905207755 @default.
- W3096810954 cites W2951268555 @default.
- W3096810954 cites W2965965865 @default.
- W3096810954 cites W2969270423 @default.
- W3096810954 cites W2979393944 @default.
- W3096810954 cites W3001459179 @default.
- W3096810954 doi "https://doi.org/10.1038/s41598-020-75646-w" @default.
- W3096810954 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7596085" @default.
- W3096810954 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33122756" @default.