Acute Regulation of Habituation Learning via Posttranslational Palmitoylation.

Acute Regulation of Habituation Learning via Posttranslational Palmitoylation.
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DOI:
10.1016/j.cub.2020.05.016
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发表时间:
2020-07-20
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Granato M
Granato M
中科院分区:
其他
文献类型:
--
作者:
Nelson JC;Witze E;Ma Z;Ciocco F;Frerotte A;Randlett O;Foskett JK;Granato M

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习惯化是一种适应性学习过程,使动物能够调整先天行为以适应环境的变化。尽管它对各种行为的影响有很好的记录,但习惯化学习的分子和细胞基础还没有得到很好的理解。使用在无偏遗传筛选中分离的斑马鱼突变体的全基因组测序,我们确定了棕榈酰转移酶亨廷顿蛋白相互作用蛋白14(Hip14)作为习惯化学习的关键调节因子。我们证明,Hip14调节抑郁症的感觉输入到一个确定的后脑神经元,并提供证据表明,Hip14 palmitoylates的摇床样K+电压门控通道亚基(Kv1.1),从而调节Kv1.1亚细胞定位。此外,我们表明,像Hip14一样,Kv1.1的丢失会导致习惯化缺陷,Hip14在发育中被抑制,而不是强烈地促进习惯化。结合起来,这些结果揭示了一个以前不受重视的作用,急性翻译后棕榈酰化在定义的电路组件,以调节学习。
Habituation is an adaptive learning process that enables animals to adjust innate behaviors to changes in their environment. Despite its well documented implications for a wide diversity of behaviors, the molecular and cellular basis of habituation learning is not well understood. Using whole genome sequencing of zebrafish mutants isolated in an unbiased genetic screen, we identified the palmitoyltransferase Huntingtin Interacting Protein 14 (Hip14) as a critical regulator of habituation learning. We demonstrate that Hip14 regulates depression of sensory inputs onto an identified hindbrain neuron and provide evidence that Hip14 palmitoylates the Shaker-like K+ voltage-gated channel subunit (Kv1.1), thereby regulating Kv1.1 subcellular localization. Furthermore, we show that like for Hip14, loss of Kv1.1 leads to habituation deficits, and that Hip14 is dispensable in development and instead acts acutely to promote habituation. Combined, these results uncover a previously unappreciated role for acute post-translational palmitoylation at defined circuit components to regulate learning.
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