The calcineurin regulator Sarah enables distinct forms of homeostatic plasticity at the Drosophila neuromuscular junction.
The calcineurin regulator Sarah enables distinct forms of homeostatic plasticity at the Drosophila neuromuscular junction.
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DOI：
10.3389/fnsyn.2022.1033743
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发表时间：
2022
影响因子：
3.7
通讯作者：
Frank, C. Andrew
中科院分区：
文献类型：
--
作者：
Armstrong, Noah S.;Frank, C. Andrew
关键词：
简介：突触维持生理水平的诱发神经传递的能力对神经元的稳定性至关重要。各种干扰都可能破坏神经传递，但突触通常会补偿干扰，并利用稳态突触可塑性的形式稳定活动水平。突触前稳态增强（PHP）就是这样一种机制。PHP在果蝇幼虫神经肌肉接头（NMJ）突触以及其他NMJ处表达。在PHP中，突触前神经递质释放增加以抵消损害肌肉递质受体的影响。之前的果蝇研究工作已经使用不同的方式来扰乱肌肉受体功能-急性（使用药理学）或慢性（使用遗传学）。我们以前的一些数据表明，细胞质钙信号是重要的表达PHP后，遗传损伤的谷氨酸受体。在这里，我们对这一观察进行了跟踪。研究方法：我们使用转基因果蝇RNA干扰和过表达品系的组合，沿着NMJ电生理学、突触成像和药理学来测试钙/钙调蛋白依赖性蛋白磷酸酶钙调磷酸酶的调节剂是否是PHP正常表达所必需的。结果：我们发现，无论是前或突触后失调的果蝇基因调节钙调磷酸酶，莎拉（sra），块PHP。组织特异性操作表明，sra表达的增加或减少对PHP有害。此外，PHP的基因表达和遗传诱导的表达形式在功能上是可分离的，这完全取决于使用哪种基因操作。令人惊讶的是，双组织突触前和突触后的sra敲低或过表达可以改善PHP块在单组织实验中发现。钙调神经磷酸酶的药理学和遗传抑制证实了后一个发现。讨论：我们的研究结果表明，在多种组织类型中需要严格的钙调磷酸酶调节来稳定外周突触输出。
Introduction: The ability of synapses to maintain physiological levels of evoked neurotransmission is essential for neuronal stability. A variety of perturbations can disrupt neurotransmission, but synapses often compensate for disruptions and work to stabilize activity levels, using forms of homeostatic synaptic plasticity. Presynaptic homeostatic potentiation (PHP) is one such mechanism. PHP is expressed at the Drosophila melanogaster larval neuromuscular junction (NMJ) synapse, as well as other NMJs. In PHP, presynaptic neurotransmitter release increases to offset the effects of impairing muscle transmitter receptors. Prior Drosophila work has studied PHP using different ways to perturb muscle receptor function—either acutely (using pharmacology) or chronically (using genetics). Some of our prior data suggested that cytoplasmic calcium signaling was important for expression of PHP after genetic impairment of glutamate receptors. Here we followed up on that observation. Methods: We used a combination of transgenic Drosophila RNA interference and overexpression lines, along with NMJ electrophysiology, synapse imaging, and pharmacology to test if regulators of the calcium/calmodulin-dependent protein phosphatase calcineurin are necessary for the normal expression of PHP. Results: We found that either pre- or postsynaptic dysregulation of a Drosophila gene regulating calcineurin, sarah (sra), blocks PHP. Tissue-specific manipulations showed that either increases or decreases in sra expression are detrimental to PHP. Additionally, pharmacologically and genetically induced forms of expression of PHP are functionally separable depending entirely upon which sra genetic manipulation is used. Surprisingly, dual-tissue pre- and postsynaptic sra knockdown or overexpression can ameliorate PHP blocks revealed in single-tissue experiments. Pharmacological and genetic inhibition of calcineurin corroborated this latter finding. Discussion: Our results suggest tight calcineurin regulation is needed across multiple tissue types to stabilize peripheral synaptic outputs.
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影响因子：
16.2
作者：
Bosch M;Castro J;Saneyoshi T;Matsuno H;Sur M;Hayashi Y
通讯作者：
Hayashi Y
DOI：
10.1073/pnas.92.1.56
发表时间：
1995-01-03
影响因子：
11.1
作者：
CLARDY, J
通讯作者：
CLARDY, J
影响因子：
5.3
作者：
Frank CA
通讯作者：
Frank CA
影响因子：
4
作者：
Aponte-Santiago NA;Littleton JT
通讯作者：
Littleton JT
影响因子：
5.3
作者：
Brusich DJ;Spring AM;Frank CA
通讯作者：
Frank CA