CAPS1 stabilizes the state of readily releasable synaptic vesicles to fusion competence at CA3-CA1 synapses in adult hippocampus.
CAPS1 stabilizes the state of readily releasable synaptic vesicles to fusion competence at CA3-CA1 synapses in adult hippocampus.
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DOI：
10.1038/srep31540
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发表时间：
2016-08-22
影响因子：
4.6
通讯作者：
Furuichi T
中科院分区：
文献类型：
--
作者：
Shinoda Y;Ishii C;Fukazawa Y;Sadakata T;Ishii Y;Sano Y;Iwasato T;Itohara S;Furuichi T
钙依赖性分泌激活蛋白1 （Calcium-dependent activator protein for secret1, CAPS1）调节神经内分泌细胞致密核囊泡和神经元突触囊泡的胞吐。然而，成熟大脑中CAPS1的突触功能尚不清楚，因为CAPS1基因敲除（KO）会导致新生儿死亡。在这里，我们使用前脑特异性Caps1条件KO （cKO）小鼠，首次证明了Caps1在成年突触中的关键作用。与对照小鼠相比，cKO小鼠急性海马切片CA3-CA1突触的突触传递幅度明显降低，配对脉冲易化显著增加，提示突触前功能受到扰动。形态学分析显示突触前有突触囊泡的积累，但总体形态学没有变化。然而，有趣的是，在Caps1 cKO中，停靠囊泡的百分比显着降低。综上所述，我们的研究结果表明，CAPS1稳定了易释放突触囊泡的状态，从而增强了海马突触的神经递质释放。
Calcium-dependent activator protein for secretion 1 (CAPS1) regulates exocytosis of dense-core vesicles in neuroendocrine cells and of synaptic vesicles in neurons. However, the synaptic function of CAPS1 in the mature brain is unclear because Caps1 knockout (KO) results in neonatal death. Here, using forebrain-specific Caps1 conditional KO (cKO) mice, we demonstrate, for the first time, a critical role of CAPS1 in adult synapses. The amplitude of synaptic transmission at CA3–CA1 synapses was strongly reduced, and paired-pulse facilitation was significantly increased, in acute hippocampal slices from cKO mice compared with control mice, suggesting a perturbation in presynaptic function. Morphological analysis revealed an accumulation of synaptic vesicles in the presynapse without any overall morphological change. Interestingly, however, the percentage of docked vesicles was markedly decreased in the Caps1 cKO. Taken together, our findings suggest that CAPS1 stabilizes the state of readily releasable synaptic vesicles, thereby enhancing neurotransmitter release at hippocampal synapses.