Synaptic memory survives molecular turnover.
Synaptic memory survives molecular turnover.
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DOI：
10.1073/pnas.2211572119
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发表时间：
2022-10-18
影响因子：
11.1
通讯作者：
Nicoll, Roger A.
中科院分区：
文献类型：
--
作者：
Lee, Joel;Chen, Xiumin;Nicoll, Roger A.
大脑如何维持比编码记忆的蛋白质更持久的记忆呢？弗朗西斯·克里克在1984年提出了一个模型，该模型由一个多聚体蛋白组成，该多聚体蛋白的亚基可以相互磷酸化，而幼稚的非活性亚基可以交换成活性的多聚体蛋白。另一种模型是，有活性的全酶可以直接将活性转移到非活性的全酶，保持全酶的完整性。最近的生化研究表明，活性的钙/钙调蛋白依赖的蛋白激酶II(CaMKII)可以将活性传递给非活性的CaMKII。在这里，我们证明，海马区突触包含在切片培养准备之前获得的CaMKII记忆痕迹，它在CaMKII蛋白完全周转(2周)后保持完好。我们的结论是，突触记忆(活性CaMKII)可以转移到新合成的幼稚CaMKII上，从而在蛋白质周转的情况下维持记忆。钙/钙调蛋白依赖的激酶II(CaMKII)的激活在长时程增强(LTP)中起着关键作用，LTP是一种公认的学习和记忆细胞模型。然而，LTP和记忆是如何在突触蛋白，特别是CaMKII的更替中幸存下来的，仍然是一个谜。在这里，我们利用了这一发现，即在切片准备之前获得的结构性钙依赖的CaMKII活性，在突触提供了持久的记忆痕迹。在切片培养中，在没有钙离子刺激的情况下，这种持续的CaMKII活性在2周内保持稳定，远远超过CaMKII蛋白的周转。我们认为，新生的CaMKII蛋白在2wk时从先前存在的活性CaMKII分子中获得其活性，这些活性分子将其活性转移到新合成的CaMKII分子上，从而在蛋白质周转时维持记忆。
How does the brain maintain memories that long outlast the proteins that encoded them? Francis Crick in 1984 proposed a model consisting of a multimeric protein whose subunits can phosphorylate each other and that naive unactive subunits can exchange into the active multimeric protein. An alternative model is that active holoenzymes can directly transfer activity to unactive holoenzymes, maintaining the integrity of the holoenzymes. Recent biochemical findings indicate that active Ca2+/calmodulin-dependent protein kinase II (CaMKII) can propagate activity to unactive CaMKII. Here, we demonstrate that hippocampal synapses contain a CaMKII memory trace acquired prior to slice culture preparation, which remains intact well after the complete turnover of CaMKII protein (2 weeks). We conclude that the synaptic memory (active CaMKII) can be transferred to naive newly synthesized CaMKII, thus sustaining the memory in the face of protein turnover. Activation of Ca2+/calmodulin-dependent kinase II (CaMKII) plays a critical role in long-term potentiation (LTP), a long accepted cellular model for learning and memory. However, how LTP and memories survive the turnover of synaptic proteins, particularly CaMKII, remains a mystery. Here, we take advantage of the finding that constitutive Ca2+-independent CaMKII activity, acquired prior to slice preparation, provides a lasting memory trace at synapses. In slice culture, this persistent CaMKII activity, in the absence of Ca2+ stimulation, remains stable over a 2-wk period, well beyond the turnover of CaMKII protein. We propose that the nascent CaMKII protein present at 2 wk acquired its activity from preexisting active CaMKII molecules, which transferred their activity to newly synthesized CaMKII molecules and thus maintain the memory in the face of protein turnover.
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影响因子：
7.7
作者：
Karandur D;Bhattacharyya M;Xia Z;Lee YK;Muratcioglu S;McAffee D;McSpadden ED;Qiu B;Groves JT;Williams ER;Kuriyan J
通讯作者：
Kuriyan J
影响因子：
16.2
作者：
Bosch M;Castro J;Saneyoshi T;Matsuno H;Sur M;Hayashi Y
通讯作者：
Hayashi Y
DOI：
10.1073/pnas.92.24.11175
发表时间：
1995-11-21
影响因子：
11.1
作者：
LLEDO, PM;HJELMSTAD, GO;NICOLL, RA
通讯作者：
NICOLL, RA
影响因子：
16.2
作者：
Barria, A;Malinow, R
通讯作者：
Malinow, R
影响因子：
7.2
作者：
Bhattacharyya, Moitrayee;Karandur, Deepti;Kuriyan, John
通讯作者：
Kuriyan, John