Naked Dense Bodies Provoke Depression

Naked Dense Bodies Provoke Depression
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DOI:
10.1523/jneurosci.2495-10.2010
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发表时间:
2010-10-27
影响因子:
5.3
通讯作者:
Heckmann, Manfred
Heckmann, Manfred
中科院分区:
医学1区
文献类型:
--
作者:
Hallermann, Stefan;Kittel, Robert J.;Heckmann, Manfred

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在突触前活动区(AZs),经常观察到的突触小泡与电子致密的细胞基质捆绑在一起的过程是一个功能意义未知的过程。在这里,我们确定了一个亚型等位基因BRP(Nude),它只缺少活动区蛋白Bruchilot的最后1%的C末端氨基酸(1740个氨基酸中的17个)。在BRP(裸鼠)中,尽管完全没有突触小泡,但电子致密小体形状正确。在基础谷氨酸释放不变的情况下,双脉冲和持续刺激会引起抑郁。此外,缓释后的快速恢复是缓慢的。我们的结果在分子内精确地将AZ细胞线上的小泡与突触抑制联系在一起。
At presynaptic active zones (AZs), the frequently observed tethering of synaptic vesicles to an electron-dense cytomatrix represents a process of largely unknown functional significance. Here, we identified a hypomorphic allele, brp(nude), lacking merely the last 1% of the C-terminal amino acids (17 of 1740) of the active zone protein Bruchpilot. In brp(nude), electron-dense bodies were properly shaped, though entirely bare of synaptic vesicles. While basal glutamate release was unchanged, paired-pulse and sustained stimulation provoked depression. Furthermore, rapid recovery following sustained release was slowed. Our results causally link, with intramolecular precision, the tethering of vesicles at the AZ cytomatrix to synaptic depression.