Regulation of exocytotic protein expression and Ca2+-dependent peptide secretion in astrocytes
Regulation of exocytotic protein expression and Ca2+-dependent peptide secretion in astrocytes
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DOI：
10.1111/j.1471-4159.2009.06116.x
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发表时间：
2009-07-01
影响因子：
4.7
通讯作者：
Aguado, Fernado
中科院分区：
文献类型：
--
作者：
Paco, Sonia;Margeli, Maria A.;Aguado, Fernado
星形胶质细胞释放囊泡递质影响神经元的发育、功能和可塑性。然而，星形胶质细胞的分泌途径和相关的分子机制知之甚少。在这项研究中，我们表明，各种SNARE和Munc 18亚型表达培养的星形胶质细胞，与syntaxin-4，Munc 18 c，SNAP-23和VAMP-3是最丰富的变体。激活剂和分化剂对胞吐蛋白的表达有不同的调节。具体而言，蛋白质控制神经内分泌细胞中的Ca 2+依赖性分泌上调后，长期的8Br-cAMP管理星形胶质细胞，但不是由促炎细胞因子。此外，8Br-cAMP处理大大增加了肽囊泡标记物分泌颗粒蛋白-2的细胞含量。对cAMP处理的星形胶质细胞进行的释放测定显示，基础和刺激的分泌颗粒蛋白-2分泌依赖于[Ca 2 +]（i）。如图所示，嵌合激素ANP.emd从转染细胞中释放，cAMP诱导的星形胶质细胞分化增强了Ca 2+调节的肽分泌。我们的结论是，星形胶质细胞显示出独特的分子组成的胞吐作用。此外，通过分化剂和活化剂调节星形胶质细胞的胞吐蛋白表达和Ca 2+依赖性肽分泌，表明胶质细胞分泌途径在不同的生理状态下进行调节。
Vesicular transmitter release from astrocytes influences neuronal development, function and plasticity. However, secretory pathways and the involved molecular mechanisms in astroglial cells are poorly known. In this study, we show that a variety of SNARE and Munc18 isoforms are expressed by cultured astrocytes, with syntaxin-4, Munc18c, SNAP-23 and VAMP-3 being the most abundant variants. Exocytotic protein expression was differentially regulated by activating and differentiating agents. Specifically, proteins controlling Ca2+-dependent secretion in neuroendocrine cells were up-regulated after long-term 8Br-cAMP administration in astrocytes, but not by proinflammatory cytokines. Moreover, 8Br-cAMP treatment greatly increased the cellular content of the peptidie vesicle marker secretogranin-2. Release assays performed on cAMP-treated astrocytes showed that basal and stimulated secretogranin-2 secretion are dependent on [Ca2+](i). As shown release of the chimeric hormone ANP.emd from transfected cells, cAMP-induced differentiation in astrocytes enhances Ca2+-regulated peptide secretion. We conclude that astroglial cells display distinctive molecular components for exocytosis. Moreover, the regulation of both exocytotic protein expression and Ca2+-dependent peptide secretion in astrocytes by differentiating and activating agents suggest that glial secretory pathways are adjusted in different physiological states.