F‐actin determines the time‐dependent shift in docking dynamics of glucagon‐like peptide‐1 granules upon stimulation of secretion

F‐actin determines the time‐dependent shift in docking dynamics of glucagon‐like peptide‐1 granules upon stimulation of secretion
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F-肌动蛋白决定胰高血糖素样肽-1颗粒在刺激分泌后对接动力学的时间依赖性变化

DOI:
10.1002/1873-3468.14580
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发表时间:
2023
期刊:
影响因子:
3.5
通讯作者:
Tsuboi Takashi
Tsuboi Takashi
中科院分区:
生物学3区
文献类型:
--
作者:
Harada Kazuki;Takashima Maoko;Kitaguchi Tetsuya;Tsuboi Takashi

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虽然胞吐作用可以根据对接动力学分为几种形式,但胞吐形式的时间调节机制尚不清楚。我们探索了小鼠GLUTag细胞中胰高血糖素样肽-1(GLP-1)胞吐的动力学(分泌GLP-1的肠内分泌L-细胞),以阐明调节不同类型胞吐形式之间平衡的机制(刺激前与质膜预对接;刺激后对接,随后融合;或在刺激后迅速募集和融合,而没有稳定的对接)。GLP-1胞吐作用显示出双相模式,我们发现大多数胞吐作用来自刺激前与质膜预对接的颗粒,或刺激后未对接的颗粒快速融合至质膜。与此相反,颗粒对接与质膜刺激后,并最终融合占主导地位。肌动蛋白聚合的抑制抑制了预对接颗粒的胞吐作用。这些结果表明,GLP-1颗粒的对接动力学显示出时间依赖性的双相转变,这是由与F-肌动蛋白的相互作用决定的。
Although exocytosis can be categorized into several forms based on docking dynamics, temporal regulatory mechanisms of the exocytotic forms are unclear. We explored the dynamics of glucagon‐like peptide‐1 (GLP‐1) exocytosis in murine GLUTag cells (GLP‐1‐secreting enteroendocrine L‐cells) upon stimulation with deoxycholic acid (DCA) or high K+to elucidate the mechanisms regulating the balance between the different types of exocytotic forms (pre‐docked with the plasma membrane before stimulation; docked after stimulation and subsequently fused; or rapidly recruited and fused after stimulation, without stable docking). GLP‐1 exocytosis showed a biphasic pattern, and we found that most exocytosis was from the pre‐docked granules with the plasma membrane before stimulation, or granules rapidly fused to the plasma membrane without docking after stimulation. In contrast, granules docked with the plasma membrane after stimuli and eventually fused were predominant thereafter. Inhibition of actin polymerization suppressed exocytosis of the pre‐docked granules. These results suggest that the docking dynamics of GLP‐1 granules shows a time‐dependent biphasic shift, which is determined by interaction with F‐actin.
抑制皮下产生胰高血糖素的 GLUTag 可移植肿瘤小鼠的胰腺胰高血糖素基因表达。
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