Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection.
Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection.
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DOI：
10.1016/j.celrep.2014.01.005
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发表时间：
2014-02-13
期刊：
影响因子：
8.8
通讯作者：
Bayer KU
中科院分区：
文献类型：
--
作者：
Coultrap SJ;Freund RK;O'Leary H;Sanderson JL;Roche KW;Dell'Acqua ML;Bayer KU
传统上，突触强度的海马长时程增强（LTP）需要Ca 2 +/钙调蛋白（CaM）依赖性蛋白激酶II（CaMKII）和其他激酶，而长时程抑制（LTD）需要磷酸酶。在这里，我们发现LTD还需要CaMKII及其磷酸化T286诱导的“自主”（Ca 2+非依赖性）活性。然而，虽然LTP已知诱导AMPA型谷氨酸受体（AMPAR）亚基GluA 1在S831处的磷酸化，但LTD反而诱导CaMKII介导的S567处的磷酸化，这是一个已知减少突触GluA 1定位的位点。GluA 1 S831磷酸化的“自主”CaMKII进一步刺激钙离子/钙调素，如预期的传统基板。相比之下，GluA 1 S567代表了一个独特的底物类，不受这种刺激的影响。这种差异调节导致GluA 1 S831受到LTP型刺激（强但短暂）的青睐，而GluA 1 S567受到LTD型刺激（弱但延长）的青睐。因此，要求自主CaMKII在相反形式的可塑性涉及不同的基板类，差异调节，使刺激依赖性的基板网站的偏好。
Traditionally, hippocampal long-term potentiation (LTP) of synaptic strength requires Ca2+/calmodulin(CaM)-dependent protein kinase II (CaMKII) and other kinases, while long-term depression (LTD) requires phosphatases. Here we found that LTD also requires CaMKII and its phospho-T286-induced “autonomous” (Ca2+-independent) activity. However, while LTP is known to induce phosphorylation of the AMPA-type glutamate receptor (AMPAR) subunit GluA1 at S831, LTD instead induced CaMKII-mediated phosphorylation at S567, a site known to reduce synaptic GluA1 localization. GluA1 S831 phosphorylation by “autonomous” CaMKII was further stimulated by Ca2+/CaM, as expected for traditional substrates. By contrast, GluA1 S567 represents a distinct substrate-class that is unaffected by such stimulation. This differential regulation caused GluA1 S831 to be favored by LTP-type stimuli (strong but brief), while GluA1 S567 was favored by LTD-type stimuli (weak but prolonged). Thus, requirement of autonomous CaMKII in opposing forms of plasticity involves distinct substrate classes that are differentially regulated to enable stimulus-dependent substrate-site preference.
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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：
34.7
作者：
Lisman, John;Yasuda, Ryohei;Raghavachari, Sridhar
通讯作者：
Raghavachari, Sridhar
影响因子：
3.7
作者：
Coultrap, Steven J.;Barcomb, Kelsey;Bayer, K. Ulrich
通讯作者：
Bayer, K. Ulrich
影响因子：
56.9
作者：
De Koninck, P;Schulman, H
通讯作者：
Schulman, H
影响因子：
5.3
作者：
Mockett, Bruce G.;Guevremont, Diane;Abraham, Wickliffe C.
通讯作者：
Abraham, Wickliffe C.