CAPS1 RNA Editing Promotes Dense Core Vesicle Exocytosis.

CAPS1 RNA Editing Promotes Dense Core Vesicle Exocytosis.
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DOI:
10.1016/j.celrep.2016.10.073
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发表时间:
2016-11-15
期刊:
影响因子:
8.8
通讯作者:
Kawahara Y
Kawahara Y
中科院分区:
生物学1区
文献类型:
--
作者:
Miyake K;Ohta T;Nakayama H;Doe N;Terao Y;Oiki E;Nagatomo I;Yamashita Y;Abe T;Nishikura K;Kumanogoh A;Hashimoto K;Kawahara Y

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钙依赖性分泌激活蛋白1 (CAPS1)在致密核囊泡(DCV)胞吐的启动步骤中起着独特的作用。已知CAPS1前mrna在其编码区进行腺苷-肌苷RNA编辑,导致其c端区域的一个位点发生谷氨酸-甘氨酸转换。然而,CAPS1 RNA编辑的生理意义尚不明确。在这里,我们创建了编辑后的CAPS1仅表达的突变小鼠。这些小鼠之所以瘦弱,是因为身体多动导致能量消耗增加。电生理和生化分析表明,DCVs在小鼠的染色质细胞和神经元中的胞吐上调。此外,我们发现编辑后的CAPS1优先结合到syntaxin-1A的活化形式,syntaxin-1A是胞外融合复合体的一个组成部分。这些发现表明,RNA编辑在体内调节DCV胞吐,影响身体活动。
Calcium-dependent activator protein for secretion 1 (CAPS1) plays a distinct role in the priming step of dense core vesicle (DCV) exocytosis. CAPS1 pre-mRNA is known to undergo adenosine-to-inosine RNA editing in its coding region, which results in a glutamate-to-glycine conversion at a site in its C-terminal region. However, the physiological significance of CAPS1 RNA editing remains elusive. Here, we created mutant mice in which edited CAPS1 was solely expressed. These mice were lean due to increased energy expenditure caused by physical hyperactivity. Electrophysiological and biochemical analyses demonstrated that the exocytosis of DCVs was upregulated in the chromaffin cells and neurons of these mice. Furthermore, we showed that edited CAPS1 bound preferentially to the activated form of syntaxin-1A, a component of the exocytotic fusion complex. These findings suggest that RNA editing regulates DCV exocytosis in vivo, affecting physical activity.
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