...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release
【24h】

Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release

机译：Doc2b通过快速刺激并抑制持续释放来同步嗜铬细胞的分泌

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Synaptotagmin-1 and -7 constitute the main calcium sensors mediating SNARE-dependent exocytosis in mouse chromaffin cells, but the role of a closely related calcium-binding protein, Doc2b, remains enigmatic. We investigated its role in chromaffin cells using Doc2b knock-out mice and high temporal resolution measurements of exocytosis. We found that the calcium dependence of vesicle priming and release triggering remained unchanged, ruling out an obligatory role for Doc2b in those processes. However, in the absence of Doc2b, release was shifted from the readily releasable pool to the subsequent sustained component. Conversely, upon overexpression of Doc2b, the sustained component was largely inhibited whereas the readily releasable pool was augmented. Electron microscopy revealed an increase in the total number of vesicles upon Doc2b overexpression, ruling out vesicle depletion as the cause for the reduced sustained component. Further experiments showed that, in the absence of Doc2b, the refilling of the readily releasable vesicle pools is faster, but incomplete. Faster refilling leads to an increase in the sustained component as newly primed vesicles fuse while the [Ca2+]i following stimulation is still high. We conclude that Doc2b acts to inhibit vesicle priming during prolonged calcium elevations, thus protecting unprimed vesicles from fusing prematurely, and redirecting them to refill the readily releasable pool after relaxation of the calcium signal. In sum, Doc2b favors fast, synchronized release, and limits out-of-phase secretion.
机译：Synaptotagmin-1和-7构成介导小鼠嗜铬细胞中SNARE依赖的胞吐作用的主要钙传感器，但密切相关的钙结合蛋白Doc2b的作用仍然难以捉摸。我们使用Doc2b基因敲除小鼠和胞吐作用的高时间分辨率测量研究了它在嗜铬细胞中的作用。我们发现囊泡引发和释放触发的钙依赖性保持不变，排除了Doc2b在这些过程中的强制性作用。但是，在不存在Doc2b的情况下，释放从易于释放的库转移到了后续的持续成分。相反，在Doc2b的过表达后，持续性成分被大大抑制，而易于释放的库则增加。电子显微镜显示，Doc2b过表达后囊泡总数增加，排除了囊泡耗竭是持续成分减少的原因。进一步的实验表明，在没有Doc2b的情况下，易于释放的囊泡池的填充速度更快，但不完全。更快的重新填充会导致持续成分的增加，因为新上等的囊泡会融合，而刺激后的[Ca2 +] i仍然很高。我们得出的结论是，Doc2b在长时间的钙升高过程中起抑制囊泡充盈的作用，从而保护未引发的囊泡免于过早融合，并在钙信号松弛后重新定向以重新填充易于释放的囊泡。总之，Doc2b支持快速，同步释放，并限制了异相分泌。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号