Palida Sakina F, Butko Margaret T, Ngo John T, Mackey Mason R, Gross Larry A, Ellisman Mark H, Tsien Roger Y
Department of Pharmacology.
Department of Pharmacology, Howard Hughes Medical Institute.
J Neurosci. 2015 May 20;35(20):7736-49. doi: 10.1523/JNEUROSCI.0004-15.2015.
Synthesizing, localizing, and stabilizing new protein copies at synapses are crucial factors in maintaining the synaptic changes required for storing long-term memories. PKMζ recently emerged as a molecule putatively responsible for maintaining encoded memories over time because its presence correlates with late LTP and because its inhibition disrupts LTP in vitro and long-term memory storage in vivo. Here we investigated PKMζ stability in rat neurons to better understand its role during information encoding and storage. We used TimeSTAMP reporters to track the synthesis and degradation of PKMζ as well as a related atypical PKC, PKCλ. These reporters revealed that both PKMζ and PKCλ were upregulated after chemical LTP induction; however, these new PKMζ copies exhibited more rapid turnover than basally produced PKMζ, particularly in dendritic spines. In contrast to PKMζ, new PKCλ copies exhibited elevated stability. Stable information storage over long periods of time is more challenging the shorter the metabolic lifetime of the candidate molecules.
在突触处合成、定位并稳定新的蛋白质拷贝是维持存储长期记忆所需突触变化的关键因素。PKMζ最近成为一种可能负责长期维持编码记忆的分子，因为它的存在与晚期长时程增强（LTP）相关，且其抑制作用在体外会破坏LTP，在体内会破坏长期记忆存储。在此，我们研究了大鼠神经元中PKMζ的稳定性，以更好地理解其在信息编码和存储过程中的作用。我们使用TimeSTAMP报告基因来追踪PKMζ以及相关的非典型蛋白激酶C（PKC）PKCλ的合成和降解。这些报告基因显示，化学诱导LTP后，PKMζ和PKCλ均上调；然而，这些新合成的PKMζ拷贝的周转速度比基础产生的PKMζ更快，尤其是在树突棘中。与PKMζ相反，新合成的PKCλ拷贝表现出更高的稳定性。候选分子的代谢寿命越短，长时间稳定的信息存储就越具挑战性。
