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肌球蛋白 1b 和 F-肌动蛋白参与了分泌颗粒生物发生的控制。

Myosin 1b and F-actin are involved in the control of secretory granule biogenesis.

机构信息

Normandie Univ, UNIROUEN, INSERM, U1239, Laboratoire de Différenciation et Communication Neuronale et Neuroendocrine, Institut de Recherche et d'Innovation Biomédicale de Normandie, 76000, Rouen, France.

Université de Strasbourg, CNRS UPR 3212, Institut des Neurosciences Cellulaires et Intégratives, 67000, Strasbourg, France.

出版信息

Sci Rep. 2017 Jul 12;7(1):5172. doi: 10.1038/s41598-017-05617-1.

Abstract

Hormone secretion relies on secretory granules which store hormones in endocrine cells and release them upon cell stimulation. The molecular events leading to hormone sorting and secretory granule formation at the level of the TGN are still elusive. Our proteomic analysis of purified whole secretory granules or secretory granule membranes uncovered their association with the actomyosin components myosin 1b, actin and the actin nucleation complex Arp2/3. We found that myosin 1b controls the formation of secretory granules and the associated regulated secretion in both neuroendocrine cells and chromogranin A-expressing COS7 cells used as a simplified model of induced secretion. We show that F-actin is also involved in secretory granule biogenesis and that myosin 1b cooperates with Arp2/3 to recruit F-actin to the Golgi region where secretory granules bud. These results provide the first evidence that components of the actomyosin complex promote the biogenesis of secretory granules and thereby regulate hormone sorting and secretion.

摘要

激素分泌依赖于储存激素的内分泌细胞中的分泌颗粒,并在细胞受到刺激时释放激素。导致 TGN 水平上激素分拣和分泌颗粒形成的分子事件仍然难以捉摸。我们对纯化的全分泌颗粒或分泌颗粒膜的蛋白质组学分析揭示了它们与肌球蛋白 1b、肌动蛋白和肌动蛋白成核复合物 Arp2/3 的关联。我们发现肌球蛋白 1b 控制神经内分泌细胞和作为诱导分泌简化模型的表达嗜铬粒蛋白 A 的 COS7 细胞中分泌颗粒的形成和相关的受调控分泌。我们表明 F-肌动蛋白也参与分泌颗粒的生物发生,并且肌球蛋白 1b 与 Arp2/3 合作将 F-肌动蛋白募集到分泌颗粒萌芽的高尔基体区域。这些结果首次提供了证据,证明肌动球蛋白复合物的成分促进了分泌颗粒的生物发生,从而调节了激素的分拣和分泌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c90/5507975/f952afc757f0/41598_2017_5617_Fig1_HTML.jpg

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