Ca2+-regulated secretory granule exocytosis in pancreatic and parotid acinar cells

Ca2+-regulated secretory granule exocytosis in pancreatic and parotid acinar cells
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DOI:
10.1016/j.ceca.2014.03.003
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发表时间:
2014-06-01
期刊:
影响因子:
4
通讯作者:
Groblewski, Guy E.
Groblewski, Guy E.
中科院分区:
生物学2区
文献类型:
--
作者:
Messenger, Scott W.;Falkowski, Michelle A.;Groblewski, Guy E.

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胰腺和腮腺腺泡细胞的蛋白质分泌受G蛋白偶联受体激活和细胞信使Ca~(2+)、二酰甘油和cAMP的产生控制。分泌颗粒(SG)的胞吐作用与神经细胞、神经内分泌细胞和内分泌细胞有一些共同的特征,这些细胞主要受细胞内钙的升高调节。然而,除了不同的信号通路外,腺泡细胞还具有类似于1微米直径的SGS(类似于突触小泡直径的30倍),对刺激的反应速度较慢(秒级对毫秒级),表现出显著的结构性分泌,在分离的腺泡中,顶膜经历顺序的复合SG-SG胞吐。胞吐作用作为最初的快速阶段进行,在3分钟后达到峰值和下降,随后是一个较长的阶段,在20-30分钟后下降到接近基础水平。研究表明,早期阶段是由钙离子触发的,涉及SG蛋白VAMP2(囊泡相关膜蛋白2)、钙离子敏感蛋白Synatotagmin 1(Syt1)和辅助蛋白Complin 2。VAMPS介导的SG胞吐和分泌期延长的调控的分子细节仍在不断涌现。在这里,我们回顾了已知的调节分子,这些调节分子影响腺泡细胞中SG拴系、对接、启动和融合的顺序胞外过程。(C)2014爱思唯尔有限公司。保留所有权利。
Protein secretion from acinar cells of the pancreas and parotid glands is controlled by G-protein coupled receptor activation and generation of the cellular messengers Ca2+, diacylglycerol and cAMP. Secretory granule (SG) exocytosis shares some common characteristics with nerve, neuroendocrine and endocrine cells which are regulated mainly by elevated cell Ca2+. However, in addition to diverse signaling pathways, acinar cells have large similar to 1 mu m diameter SGs (similar to 30 fold larger diameter than synaptic vesicles), respond to stimulation at slower rates (seconds versus milliseconds), demonstrate significant constitutive secretion, and in isolated acini, undergo sequential compound SG-SG exocytosis at the apical membrane. Exocytosis proceeds as an initial rapid phase that peaks and declines over 3 min followed by a prolonged phase that decays to near basal levels over 20-30 min. Studies indicate the early phase is triggered by Ca2+ and involves the SG proteins VAMP2 (vesicle associated membrane protein2), Ca2+-sensing protein synatotagmin 1 (syt1) and the accessory protein complexin 2. The molecular details for regulation of VAMPS-mediated SG exocytosis and the prolonged phase of secretion are still emerging. Here we review the known regulatory molecules that impact the sequential exocytic process of SG tethering, docking, priming and fusion in acinar cells. (C) 2014 Elsevier Ltd. All rights reserved.