GluN2B S1303 phosphorylation by CaMKII or DAPK1: no indication for involvement in ischemia or LTP.
GluN2B S1303 phosphorylation by CaMKII or DAPK1: no indication for involvement in ischemia or LTP.
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DOI：
10.1016/j.isci.2021.103214
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发表时间：
2021-10-22
期刊：
影响因子：
5.8
通讯作者：
Bayer KU
中科院分区：
文献类型：
--
作者：
Tullis JE;Buonarati OR;Coultrap SJ;Bourke AM;Tiemeier EL;Kennedy MJ;Herson PS;Bayer KU
两种不同的CaM激酶CaMKII和DAPK 1与S1303附近的NMDA型谷氨酸受体（NMDAR）亚基GluN 2B的结合与兴奋性毒性/缺血性神经元细胞死亡有关。GluN 2B ΔCaMKII突变（L1298 A，R1300 Q）具有神经保护作用，但仅消除CaMKII，而不消除DAPK 1结合。然而，这两种激酶都可以额外磷酸化GluN 2B S1303。因此，我们在此测试了S1303磷酸化对神经元细胞死亡的可能贡献。GluN 2B ΔCaMKII突变完全消除了CaMKII和DAPK 1的磷酸化，表明该突变可以通过破坏磷酸化介导神经保护作用。然而，在海马脑片兴奋性毒性损伤或在体内心脏骤停和心肺复苏诱导的全脑缺血中，S1303磷酸化没有增加。在海马培养物中，化学LTD诱导S1303磷酸化，但不诱导LTP刺激。这些结果表明，GluN 2B ΔCaMKII突变对磷酸化的额外影响只需要在LTD中考虑，而不是在LTP或缺血/兴奋性毒性中考虑。神经保护性GluN 2B突变阻断了CaMK II和DAPK 1对S1303的磷酸化作用GluN 2B S1303是CaMK II比DAPK 1更好的磷酸化底物在cLTD后检测到磷酸化S1303增加，但在cLTP或兴奋性毒性刺激后未检测到磷酸化S1303增加在体内全脑缺血后未检测到磷酸化S1303生物化学;分子生物学;神经科学
Binding of two different CaM kinases, CaMKII and DAPK1, to the NMDA-type glutamate receptor (NMDAR) subunit GluN2B near S1303 has been implicated in excitotoxic/ischemic neuronal cell death. The GluN2BΔCaMKII mutation (L1298A, R1300Q) is neuroprotective but abolishes only CaMKII but not DAPK1 binding. However, both kinases can additionally phosphorylate GluN2B S1303. Thus, we here tested S1303 phosphorylation for possible contribution to neuronal cell death. The GluN2BΔCaMKII mutation completely abolished phosphorylation by CaMKII and DAPK1, suggesting that the mutation could mediate neuroprotection by disrupting phosphorylation. However, S1303 phosphorylation was not increased by excitotoxic insults in hippocampal slices or by global cerebral ischemia induced by cardiac arrest and cardiopulmonary resuscitation in vivo. In hippocampal cultures, S1303 phosphorylation was induced by chemical LTD but not LTP stimuli. These results indicate that the additional effect of the GluN2BΔCaMKII mutation on phosphorylation needs to be considered only in LTD but not in LTP or ischemia/excitotoxicity. A neuroprotective GluN2B mutation blocked S1303 phosphorylation by CaMKII and DAPK1 GluN2B S1303 is a better substrate for phosphorylation by CaMKII than by DAPK1 Increased phospho-S1303 was detected after cLTD but not cLTP or excitotoxic stimuli Increased phospho-S1303 was not detected after global cerebral ischemia in vivo Biochemistry; Molecular biology; Neuroscience
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DOI：
10.1073/pnas.89.10.4363
发表时间：
1992-05-15
影响因子：
11.1
作者：
DUDEK, SM;BEAR, MF
通讯作者：
BEAR, MF
影响因子：
8.2
作者：
Coultrap, Steven J.;Vest, Rebekah S.;Ashpole, Nicole M.;Hudmon, Andy;Bayer, K. Ulrich
通讯作者：
Bayer, K. Ulrich
DOI：
10.1111/ejn.12683
发表时间：
2014-10
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Orfila JE;Shimizu K;Garske AK;Deng G;Maylie J;Traystman RJ;Quillinan N;Adelman JP;Herson PS
通讯作者：
Herson PS
影响因子：
8.8
作者：
Hiester BG;Bourke AM;Sinnen BL;Cook SG;Gibson ES;Smith KR;Kennedy MJ
通讯作者：
Kennedy MJ
影响因子：
8.8
作者：
McKay S;Ryan TJ;McQueen J;Indersmitten T;Marwick KFM;Hasel P;Kopanitsa MV;Baxter PS;Martel MA;Kind PC;Wyllie DJA;O'Dell TJ;Grant SGN;Hardingham GE;Komiyama NH
通讯作者：
Komiyama NH