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首页> 外文期刊>Journal of Cell Science >Chromogranin B regulates early-stage insulin granule trafficking from the Golgi in pancreatic islet beta-cells
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Chromogranin B regulates early-stage insulin granule trafficking from the Golgi in pancreatic islet beta-cells

机译:ChaCrogranin B调节从胰岛β细胞中从Golgi的早期胰岛素颗粒贩运

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摘要

Chromogranin B (CgB, also known as CHGB) is abundantly expressed in dense core secretory granules of multiple endocrine tissues and has been suggested to regulate granule biogenesis in some cell types, including the pancreatic islet beta-cell, though the mechanisms are poorly understood. Here, we demonstrate a critical role for CgB in regulating secretory granule trafficking in the beta-cell. Loss of CgB impairs glucose-stimulated insulin secretion, impedes proinsulin processing to yield increased proinsulin content, and alters the density of insulin-containing granules. Using an in situ fluorescent pulse-chase strategy to track nascent proinsulin, we show that loss of CgB impairs Golgi budding of proinsulin-containing secretory granules, resulting in a substantial delay in trafficking of nascent granules to the plasma membrane with an overall decrease in total plasmamembrane-associated granules. These studies demonstrate that CgB is necessary for efficient trafficking of secretory proteins into the budding granule, which impacts the availability of insulin-containing secretory granules for exocytic release.
机译:嗜铬粒蛋白B(CGB,也称为CHGB)在多发性内分泌组织的致密核心分泌颗粒大量表达,并已建议调节在某些细胞类型,包括胰岛β细胞颗粒生物发生,虽然机制知之甚少。这里,我们证明在β细胞调节分泌颗粒贩运CGB了至关重要的作用。 CGB也妨碍葡萄糖刺激的胰岛素分泌的损失,阻止胰岛素原处理,得到增加的胰岛素原的内容,并改变含有胰岛素的颗粒的密度。使用原位荧光脉冲追踪策略来追踪新生胰岛素原,我们显示的CGB也妨碍高尔基出芽含有胰岛素原分泌颗粒,从而产生相当大的延迟在初生颗粒投放到质膜,在总的总体降低该损失质膜相关的颗粒。这些研究表明,CGB是必要的分泌蛋白的高效的广告投放到出芽颗粒,这会影响用于胞吐释放含有胰岛素的分泌颗粒的可用性。

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