LTP induction by structural rather than enzymatic functions of CaMKII.
LTP induction by structural rather than enzymatic functions of CaMKII.
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DOI：
10.1038/s41586-023-06465-y
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发表时间：
2023-09
期刊：
影响因子：
64.8
通讯作者：
Bayer, K. Ulrich
中科院分区：
文献类型：
--
作者：
Tullis, Jonathan E.;Larsen, Matthew E.;Rumian, Nicole L.;Freund, Ronald K.;Boxer, Emma E.;Brown, Carolyn Nicole;Coultrap, Steven J.;Schulman, Howard;Aoto, Jason;Dell'Acqua, Mark L.;Bayer, K. Ulrich
学习和记忆被认为需要海马长时程增强（LTP），并且三十多年来一直无可争议的分子神经科学的少数中心法则之一是LTP诱导需要Ca 2 +/钙调蛋白依赖性蛋白激酶II（CaMKII）的酶活性。然而，正如我们在这里描述的那样，实验证据令人惊讶地远非结论性的。所有以前的干预抑制酶促CaMKII活性和LTP也干扰结构CaMKII的作用，特别是结合NMDA型谷氨酸受体亚基GluN 2B。因此，我们在这里的特点，并利用互补的新的光学/药物遗传工具，以区分酶和结构CaMKII功能。几个独立的证据表明，LTP诱导的结构功能的CaMKII，而不是其酶活性。激酶活性的唯一贡献是通过T286自磷酸化自动调节这种结构作用，这解释了为什么这种区别几十年来一直难以捉摸。直接启动的结构功能的方式，规避这种T286的作用是足以引起强大的LTP，即使酶促CaMKII活性被阻断。几个独立的证据表明，长时程增强诱导钙调蛋白依赖性蛋白激酶II的结构功能，而不是其酶活性。
Learning and memory are thought to require hippocampal long-term potentiation (LTP), and one of the few central dogmas of molecular neuroscience that has stood undisputed for more than three decades is that LTP induction requires enzymatic activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII). However, as we delineate here, the experimental evidence is surprisingly far from conclusive. All previous interventions inhibiting enzymatic CaMKII activity and LTP also interfere with structural CaMKII roles, in particular binding to the NMDA-type glutamate receptor subunit GluN2B. Thus, we here characterized and utilized complementary sets of new opto-/pharmaco-genetic tools to distinguish between enzymatic and structural CaMKII functions. Several independent lines of evidence demonstrated LTP induction by a structural function of CaMKII rather than by its enzymatic activity. The sole contribution of kinase activity was autoregulation of this structural role via T286 autophosphorylation, which explains why this distinction has been elusive for decades. Directly initiating the structural function in a manner that circumvented this T286 role was sufficient to elicit robust LTP, even when enzymatic CaMKII activity was blocked. Several independent lines of evidence demonstrated long-term potentiation induction by a structural function of calmodulin-dependent protein kinase II rather than by its enzymatic activity.
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影响因子：
16.2
作者：
Barria, A;Malinow, R
通讯作者：
Malinow, R
影响因子：
8.8
作者：
Coultrap SJ;Freund RK;O'Leary H;Sanderson JL;Roche KW;Dell'Acqua ML;Bayer KU
通讯作者：
Bayer KU
DOI：
10.1016/j.bbrc.2009.10.107
发表时间：
2009-12-25
影响因子：
3.1
作者：
Bostrom, S. Lynn;Dore, Justin;Griffith, Leslie C.
通讯作者：
Griffith, Leslie C.
CaMKII 与 GluN2B 的结合在记忆巩固过程中至关重要
影响因子：
11.4
作者：
Halt, Amy R.;Dallapiazza, Robert F.;Hell, Johannes W.
通讯作者：
Hell, Johannes W.
影响因子：
8.8
作者：
Buonarati, Olivia R.;Cook, Sarah G.;Bayer, K. Ulrich
通讯作者：
Bayer, K. Ulrich