Distinct molecular pathways govern presynaptic homeostatic plasticity.
Distinct molecular pathways govern presynaptic homeostatic plasticity.
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DOI：
10.1016/j.celrep.2021.110105
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发表时间：
2021-12-14
期刊：
影响因子：
8.8
通讯作者：
Müller M
中科院分区：
文献类型：
--
作者：
Nair AG;Muttathukunnel P;Müller M
突触前稳态可塑性(PHP)通过神经递质释放增强来对抗受损的神经递质受体功能，从而稳定突触传递。PHP被认为是由受体功能受损引发的，并涉及一种刻板的信号通路。然而，在这里，我们证明了同样减少突触传递的不同受体扰动在果蝇神经肌肉接头处导致不同的反应。谷氨酸受体(GluR)拮抗剂γ-D-谷氨酰甘氨酸(γ-DGG)对受体的抑制作用不能被苯丙氨酸补偿，而GluR抑制剂Philanthooxin433(PhTx)和Gyki-53655(Gyki)则诱导代偿性PHP值。有趣的是，由PhTx和Gyki触发的PHP涉及可分离的信号通路，包括抑制不同的Glur亚型，对活动区支架BruchPilot的差异调制，以及短期可塑性。此外，虽然Gyki治疗中的PHP不需要促进PhTx诱导的PHP的基因，但它涉及突触前蛋白激酶D。因此，突触不仅对类似的活动损伤做出不同的反应，而且通过不同的机制实现稳态补偿，突显了稳态信号的多样性。突触前稳态可塑性(PHP)在几秒钟内被诱导和逆转，谷氨酸受体本身的抑制不足以诱导PHP，不同的谷氨酸受体拮抗剂触发不同的分子PHP通路，突触通过稳态神经递质释放增强来抵消神经递质受体的扰动。动态平衡补偿被认为是由受体功能受损触发的，并涉及一种刻板的信号通路。Nair等人。这里展示了不同的谷氨酸受体拮抗剂在果蝇神经肌肉连接处触发不同的动态平衡信号通路。
Presynaptic homeostatic plasticity (PHP) stabilizes synaptic transmission by counteracting impaired neurotransmitter receptor function through neurotransmitter release potentiation. PHP is thought to be triggered by impaired receptor function and to involve a stereotypic signaling pathway. However, here we demonstrate that different receptor perturbations that similarly reduce synaptic transmission result in different responses at the Drosophila neuromuscular junction. While receptor inhibition by the glutamate receptor (GluR) antagonist γ-D-glutamylglycine (γDGG) is not compensated by PHP, the GluR inhibitors Philanthotoxin-433 (PhTx) and Gyki-53655 (Gyki) induce compensatory PHP. Intriguingly, PHP triggered by PhTx and Gyki involve separable signaling pathways, including inhibition of distinct GluR subtypes, differential modulation of the active-zone scaffold Bruchpilot, and short-term plasticity. Moreover, while PHP upon Gyki treatment does not require genes promoting PhTx-induced PHP, it involves presynaptic protein kinase D. Thus, synapses not only respond differentially to similar activity impairments, but achieve homeostatic compensation via distinct mechanisms, highlighting the diversity of homeostatic signaling. Presynaptic homeostatic plasticity (PHP) is induced and reversed within seconds Glutamate receptor inhibition per se is not sufficient for PHP induction Different glutamate receptor antagonists trigger distinct molecular PHP pathways Synapses counteract neurotransmitter receptor perturbations by homeostatic neurotransmitter release potentiation. Homeostatic compensation is thought to be triggered by impaired receptor function, and to involve a stereotypic signaling pathway. Nair et al. here show that different glutamate receptor antagonists trigger distinct homeostatic signaling pathways at the Drosophila neuromuscular junction.
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影响因子：
8.8
作者：
Kiragasi, Beril;Wondolowski, Joyce;Dickman, Dion K.
通讯作者：
Dickman, Dion K.
影响因子：
16.2
作者：
Haghighi, AP;McCabe, BD;Goodman, CS
通讯作者：
Goodman, CS
影响因子：
15.9
作者：
Clements, JD;Silver, RA
通讯作者：
Silver, RA
影响因子：
7.7
作者：
James, Thomas D.;Zwiefelhofer, Danielle J.;Frank, C. Andrew
通讯作者：
Frank, C. Andrew
DOI：
10.1126/science.1179685
发表时间：
2009-11-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dickman DK;Davis GW
通讯作者：
Davis GW