Differential targeting of dynamin-1 and dynamin-3 to nerve terminals during chronic suppression of neuronal activity.
Differential targeting of dynamin-1 and dynamin-3 to nerve terminals during chronic suppression of neuronal activity.
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DOI：
10.1016/j.mcn.2015.03.016
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Halpain S
中科院分区：
文献类型：
--
作者：
Calabrese B;Halpain S
神经元表达三种密切相关的动力蛋白基因。动力蛋白1长期以来被认为与神经末梢突触囊泡循环的调节有关，而动力蛋白2和动力蛋白3最近也被证明以特定和可区分的方式促进突触囊泡循环。在培养的海马神经元中，我们发现自发网络活动的慢性抑制对内源性动力蛋白1和3靶向神经末梢有差异调节，而动力蛋白2不受影响。具体而言，当河豚毒素（TTX）长期沉默神经活动1 - 2周时，神经末梢动力蛋白1的聚集性降低，而动力蛋白3的聚集性显著增加。此外，持续阻断AMPA受体可在数小时内诱导dynamin 3聚集，提示AMPA受体可能具有阻止Dyn3在神经末梢积聚的功能。动力蛋白3的聚集是由钙依赖性蛋白磷酸酶钙调磷酸酶的拮抗剂诱导的，但不依赖于完整的肌动蛋白丝。ttx诱导的Dyn3聚集发生的时间过程明显慢于先前描述的突触蛋白1聚集。钾诱导的去极化在几分钟内迅速地将神经末梢的动力蛋白3分离。这些结果表明，这三种动力蛋白已经进化出不同的调节机制，以应对神经活动的变化，进出神经末梢。
Neurons express three closely related dynamin genes. Dynamin 1 has long been implicated in the regulation of synaptic vesicle recycling in nerve terminals, and dynamins 2 and 3 were more recently shown also to contribute to synaptic vesicle recycling in specific and distinguishable ways. In cultured hippocampal neurons we found that chronic suppression of spontaneous network activity differentially regulated the targeting of endogenous dynamins 1 and 3 to nerve terminals, while dynamin 2 was unaffected. Specifically, when neural activity was chronically silenced for 1–2 weeks by tetrodotoxin (TTX), the clustering of dynamin 1 at nerve terminals was reduced, while the clustering of dynamin 3 significantly increased. Moreover, dynamin 3 clustering was induced within hours by the sustained blockade of AMPA receptors, suggesting that AMPA receptors may function to prevent Dyn3 accumulation within nerve terminals. Clustering of dynamin 3 was induced by an antagonist of the calcium-dependent protein phosphatase calcineurin, but was not dependent upon intact actin filaments. TTX-induced clustering of Dyn3 occurred with a markedly slower time-course than the previously described clustering of synapsin 1. Potassium-induced depolarization rapidly de-clustered dynamin 3 from nerve terminals within minutes. These results, which have implications for homeostatic synapse restructuring, indicate that the three dynamins have evolved different regulatory mechanisms for trafficking to and from nerve terminals in response to changes in neural activity.