Nuclear translocation of jacob in hippocampal neurons after stimuli inducing long-term potentiation but not long-term depression.
Nuclear translocation of jacob in hippocampal neurons after stimuli inducing long-term potentiation but not long-term depression.
复制标题
刺激后海马神经元中雅各布的核易位诱导长期增强而不是长期抑制
DOI：
10.1371/journal.pone.0017276
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发表时间：
2011-02-18
期刊：
影响因子：
3.7
通讯作者：
Kreutz MR
中科院分区：
文献类型：
--
作者：
Behnisch T;Yuanxiang P;Bethge P;Parvez S;Chen Y;Yu J;Karpova A;Frey JU;Mikhaylova M;Kreutz MR
背景近年来，一些潜在的突触核蛋白信使被认为参与可塑性相关基因的表达，并具有导入蛋白介导和活性依赖的核输入的能力。然而，令人惊讶的是，很少有数据表明这种蛋白质在学习和记忆的细胞模型中是核输入的。最近才发现，转录因子cAMP反应元件结合蛋白2(CREB2)在长时抑制(LTD)时进入细胞核，而不是在突触传递的长时程增强(LTP)期间。雅各布是另一个将NMDA受体活性与核基因表达联系起来的信使。因此，我们的目的是研究在活动依赖突触可塑性的生理相关模型中Jacob是否在细胞核内积聚。方法/主要发现我们已经分析了在大鼠海马片的Schaffer侧支-CA1突触诱导NMDA受体依赖的LTP或LTD后Jacob核输入的动力学。通过对表达Jacob-Green荧光蛋白的神经元的时间推移成像，我们发现Jacob在LTP的破伤期就已经从树突快速移位到细胞核，但在LTP诱导后不是这样。免疫细胞化学染色证实，与LTP诱导后的顶端树突相比，内源性Jacob有核积累，但LTP诱导后没有。在诱导NMDA受体依赖的化学物质LTP和LTD后，在海马区的初级神经元中获得了互补的结果。然而，与以前的研究一致，高浓度的NMDA和甘氨酸以及类似病理条件的突触外NMDA受体的特异性激活导致核Jacob水平更显著的增加。结论/意义综上所述，这些发现表明，NMDA受体依赖性突触可塑性的两种主要形式LTP和LTD诱导了不同的突触-核信使的转变，尽管这两种情况下都需要Importin介导的逆行运输和NMDA受体的激活。
Background In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and that have the capacity of importin- mediated and activity-dependent nuclear import. However, there is a surprising paucity of data showing the nuclear import of such proteins in cellular models of learning and memory. Only recently it was found that the transcription factor cyclic AMP response element binding protein 2 (CREB2) transits to the nucleus during long-term depression (LTD), but not during long-term potentiation (LTP) of synaptic transmission in hippocampal primary neurons. Jacob is another messenger that couples NMDA-receptor-activity to nuclear gene expression. We therefore aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity. Methodology/Principal Findings We have analyzed the dynamics of Jacob's nuclear import following induction of NMDA-receptor dependent LTP or LTD at Schaffer collateral-CA1 synapses in rat hippocampal slices. Using time-lapse imaging of neurons expressing a Jacob-Green-Fluorescent-Protein we found that Jacob rapidly translocates from dendrites to the nucleus already during the tetanization period of LTP, but not after induction of LTD. Immunocytochemical stainings confirmed the nuclear accumulation of endogenous Jacob in comparison to apical dendrites after induction of LTP but not LTD. Complementary findings were obtained after induction of NMDA-receptor dependent chemical LTP and LTD in hippocampal primary neurons. However, in accordance with previous studies, high concentrations of NMDA and glycine as well as specific activation of extrasynaptic NMDA-receptors resembling pathological conditions induce an even more profound increase of nuclear Jacob levels. Conclusions/Significance Taken together, these findings suggest that the two major forms of NMDA-receptor dependent synaptic plasticity, LTP and LTD, elicit the transition of different synapto-nuclear messengers albeit in both cases importin-mediated retrograde transport and NMDA-receptor activation is required.
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影响因子：
9.8
作者：
Dieterich, Daniela C.;Karpova, Anna;Mikhaylova, Marina;Zdobnova, Irina;Koenig, Imbritt;Landwehr, Marco;Kreutz, Martin;Smalla, Karl-Heinz;Richter, Karin;Landgraf, Peter;Reissner, Carsten;Boeckers, Tobias M.;Zuschratter, Werner;Spilker, Christina;Seidenbecher, Constanze I.;Garner, Craig C.;Gundelfinger, Eckart D.;Kreutz, Michael R.
通讯作者：
Kreutz, Michael R.
DOI：
10.1073/pnas.0803906105
发表时间：
2008-11-04
影响因子：
11.1
作者：
Lai, Kwok-On;Zhao, Yali;Martin, Kelsey C.
通讯作者：
Martin, Kelsey C.
影响因子：
4.8
作者：
Fagerlund, Riku;Melen, Krister;Julkunen, Ilkka
通讯作者：
Julkunen, Ilkka
影响因子：
25
作者：
Hardingham, GE;Fukunaga, Y;Bading, H
通讯作者：
Bading, H
影响因子：
16.2
作者：
Lu, WY;Man, HY;Wang, YT
通讯作者：
Wang, YT