Drep-2 is a novel synaptic protein important for learning and memory.
Drep-2 is a novel synaptic protein important for learning and memory.
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DOI：
10.7554/elife.03895
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发表时间：
2014-11-13
期刊：
影响因子：
7.7
通讯作者：
Sigrist SJ
中科院分区：
文献类型：
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作者：
Andlauer TF;Scholz-Kornehl S;Tian R;Kirchner M;Babikir HA;Depner H;Loll B;Quentin C;Gupta VK;Holt MG;Dipt S;Cressy M;Wahl MC;Fiala A;Selbach M;Schwärzel M;Sigrist SJ
CIDE-N结构域介导DNA酶Dff 40/CAD及其抑制剂Dff 45/ICAD之间的相互作用。在这项研究中，我们报告说，CIDE-N蛋白Drep-2是一种新的突触蛋白的学习和行为适应的重要。Drep-2被发现在整个果蝇大脑的突触，并强烈富集在蘑菇体输入突触。它需要在凯尼恩细胞正常的嗅觉短期和中期记忆。Drep-2与代谢型谷氨酸受体（mGluRs）共定位。mGluRs的慢性药理学刺激补偿drep-2学习缺陷，并且drep-2和mGluR学习表型表现为非加和性，表明Drep 2可能参与有效的mGluR信号传导。事实上，果蝇脆性X蛋白突变体，从mGluR信号的衰减中受益，从dREP-2的消除中获益。因此，Drep-2是一种新的调节性突触因子，可能与代谢型信号传导和翻译调节交叉。DOI：http://dx.doi.org/10.7554/eLife.03895.001突触是一种特殊的结构，它将神经细胞彼此连接起来，并允许信息在细胞之间传递。突触对于学习和存储记忆至关重要。许多调节信号如何在突触上传递的蛋白质已经被研究过了。通过这种方式，人们对它们在学习和记忆中的功能有了很多了解。细胞可以通过一种称为凋亡的过程自杀，也称为程序性细胞死亡。细胞凋亡不仅在受损细胞中触发，而且对于生物体的正确发育也是必要的。在果蝇中，蛋白Drep-2是降解经历凋亡的细胞的DNA的蛋白质家族的成员。Andlauer等人没有发现Drep-2在细胞凋亡中起作用的证据，但现在已经在果蝇的大脑突触中发现了Drep-2。Drep-2可以在另一种称为代谢型谷氨酸受体的蛋白质附近观察到。代谢型谷氨酸受体及其信号通路对于调节介导学习过程的突触的某些变化是重要的。事实上，Andlauer等人发现，失去产生Drep-2的基因的果蝇在受到惩罚时无法记住气味。用药物刺激调节性谷氨酸受体有助于克服由于缺乏Drep-2而导致的学习缺陷。一种叫做FMRP的蛋白质产生的改变会导致人类脆性X综合征，这是一种最常见的遗传性精神残疾，源于单基因缺陷。缺乏FMRP蛋白的果蝇表现出学习缺陷，这与不能产生Drep-2的果蝇非常相似。然而，Andlauer等人观察到缺乏Drep-2和FMRP的果蝇可以正常学习。Drep-2在突触中如何帮助记忆形成还有待发现，尽管有迹象表明它增强了谷氨酸受体的信号作用并抵消了FMRP。还需要进一步的研究来确定与Drep-2相关的哺乳动物蛋白质是否在哺乳动物的大脑中发挥类似的作用。DOI：http://dx.doi.org/10.7554/eLife.03895.002网站
CIDE-N domains mediate interactions between the DNase Dff40/CAD and its inhibitor Dff45/ICAD. In this study, we report that the CIDE-N protein Drep-2 is a novel synaptic protein important for learning and behavioral adaptation. Drep-2 was found at synapses throughout the Drosophila brain and was strongly enriched at mushroom body input synapses. It was required within Kenyon cells for normal olfactory short- and intermediate-term memory. Drep-2 colocalized with metabotropic glutamate receptors (mGluRs). Chronic pharmacological stimulation of mGluRs compensated for drep-2 learning deficits, and drep-2 and mGluR learning phenotypes behaved non-additively, suggesting that Drep 2 might be involved in effective mGluR signaling. In fact, Drosophila fragile X protein mutants, shown to benefit from attenuation of mGluR signaling, profited from the elimination of drep-2. Thus, Drep-2 is a novel regulatory synaptic factor, probably intersecting with metabotropic signaling and translational regulation. DOI: http://dx.doi.org/10.7554/eLife.03895.001 Synapses are specialized structures that connect nerve cells to one another and allow information to be transmitted between the cells. Synapses are essential for learning and storing memories. Many proteins that regulate how signals are transmitted at synapses have already been studied. In this manner, much has been learned about their function in learning and memory. Cells can commit suicide by a process called apoptosis, also known as programmed cell death. Apoptosis is not only triggered in damaged cells but is also necessary for an organism to develop correctly. In fruit flies, the protein Drep-2 is a member of a family of proteins that degrade the DNA of cells that undergo apoptosis. Andlauer et al. found no evidence that Drep-2 plays a role in apoptosis, but have now found Drep-2 at the synapses of the brain of the fruit fly Drosophila. Drep-2 could be observed in close proximity to another type of protein called metabotropic glutamate receptors. Metabotropic glutamate receptors and their signaling pathways are important for regulating certain changes to the synapses that mediate learning processes. Indeed, Andlauer et al. found that flies that have lost the gene that produces Drep-2 were unable to remember smells when these were paired with a punishment. Stimulating the regulatory glutamate receptors with drugs helped to overcome learning deficits that result from the lack of Drep-2. Alterations in the production of a protein called FMRP cause fragile X syndrome in humans, the most common form of hereditary mental disability originating from a single gene defect. Flies lacking the FMRP protein show learning deficits that are very similar to the ones seen in flies that cannot produce Drep-2. However, Andlauer et al. observed that flies lacking both Drep-2 and FMRP can learn normally. Exactly how Drep-2 works in synapses to help with memory formation remains to be discovered, although there are indications that it boosts the effects of signaling from the glutamate receptors and counteracts FMRP. Further research will be needed to establish whether the mammalian proteins related to Drep-2 perform similar roles in the brains of mammals. DOI: http://dx.doi.org/10.7554/eLife.03895.002