Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity.
Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity.
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DOI：
10.1186/s13041-020-00691-5
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发表时间：
2020-11-10
期刊：
影响因子：
3.6
通讯作者：
Abel T
中科院分区：
文献类型：
--
作者：
Park AJ;Shetty MS;Baraban JM;Abel T
活动依赖的局部蛋白质合成对突触特异性、持久性可塑性至关重要。局部蛋白质合成异常与精神疾病有关。我们最近发现translin/trax microrna降解酶是激活突触中蛋白质合成的一种新的介质。此外，缺乏translin/trax的translin敲除（KO）小鼠在脆性X综合征小鼠模型（脆性X智力迟钝蛋白- fmrp -KO小鼠）中表现出一些行为异常。因此，确定与translin/trax相互作用的信号通路以支持持久的突触可塑性是翻译相关的目标。在这里，作为实现这一目标的第一步，我们评估了translin/trax对依赖于不同分子机制的多种海马突触可塑性范式的需求。我们发现缺乏translin/trax的小鼠表现出持续海马可塑性的选择性损伤，这需要突触后蛋白激酶a （PKA）活性。相比之下，依赖于突触前PKA的持久形式的可塑性不受影响。此外，这些小鼠没有表现出过度的代谢性谷氨酸受体介导的长期突触抑制（mGluR-LTD），这是FMRP KO小鼠的标志。相反，translin KO小鼠表现出n -甲基-d-天冬氨酸受体（NMDAR）依赖性LTD的缺陷，这一表型在FMRP敲除中未观察到。综上所述，这些发现表明translin/trax介导了依赖于突触后PKA信号的长期突触可塑性，并表明translin/trax和FMRP在海马突触可塑性中发挥了不同的作用。
Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, translin knockout (KO) mice, which lack translin/trax, exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome (fragile X mental retardation protein-FMRP-KO mice). Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic protein kinase A (PKA) activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression (mGluR-LTD), a hallmark of the FMRP KO mice. On the contrary, translin KO mice exhibited deficits in N-methyl-d-aspartate receptor (NMDAR) dependent LTD, a phenotype not observed in the FMRP knockouts. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling and suggest that translin/trax and FMRP play distinct roles in hippocampal synaptic plasticity.
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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：
5.3
作者：
Duffy, SN;Nguyen, PV
通讯作者：
Nguyen, PV
影响因子：
2.9
作者：
Luo Y;Na Z;Slavoff SA
通讯作者：
Slavoff SA
影响因子：
5.3
作者：
Chennathukuzhi, V;Stein, JM;Hecht, NB
通讯作者：
Hecht, NB
影响因子：
5.3
作者：
Bayazitov, Ildar T.;Richardson, Robert J.;Zakharenko, Stanislav S.
通讯作者：
Zakharenko, Stanislav S.