日本东京大学Haruo Kasai研究组揭示树突棘增大对突触前胞吐的机械作用。这一成果由这一研究成果于2021年11月24日发表在国际顶尖学术期刊《自然》上。
他们展示大鼠切片培养制剂中，用玻璃移液管对突触前按钮的精细和瞬时推动显著促进了谷氨酸的诱发释放和 SNARE（可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体）蛋白的组装，这通过 Förster 共振转移 (FRET) 和荧光寿命成像测量。这两种影响都持续了超过 20 分钟。突触前 FRET 增加不依赖于胞质钙 (Ca2+)，但依赖于圈套中 SNARE 蛋白的组装和肌动蛋白聚合。
值得注意的是，高渗蔗糖溶液 (20 mM) 对 FRET 和诱发释放均具有促进作用，但不会引起自发释放，这与高渗蔗糖溶液 (300 mM) 形成鲜明对比，后者本身诱导胞吐作用。最后，双光子谷氨酸解笼引起的脊柱扩大，仅当脊柱通过伸长推动扣环时才会增强诱发释放和 FRET。因此，他们在突触前按钮中确定了一种机械感觉和转导机制，其中谷氨酸的诱发释放增强了超过 20 分钟。
研究人员表示，突触传递涉及两个神经元之间突触连接处的细胞间通讯，这一过程的化学和电学形式已被广泛研究。在大脑中，兴奋性谷氨酸能突触通常在学习过程中扩大的树突棘上产生。由于树突棘和突触前末梢与突触间隙紧密相连，增大可能对突触前功能产生机械影响。
附：英文原文
Title: Mechanical actions of dendritic-spine enlargement on presynaptic exocytosis
Author: Ucar, Hasan, Watanabe, Satoshi, Noguchi, Jun, Morimoto, Yuichi, Iino, Yusuke, Yagishita, Sho, Takahashi, Noriko, Kasai, Haruo
Issue&Volume: 2021-11-24
Abstract: Synaptic transmission involves cell-to-cell communication at the synaptic junction between two neurons, and chemical and electrical forms of this process have been extensively studied. In the brain, excitatory glutamatergic synapses are often made on dendritic spines that enlarge during learning1,2,3,4,5. As dendritic spines and the presynaptic terminals are tightly connected with the synaptic cleft6, the enlargement may have mechanical effects on presynaptic functions7. Here we show that fine and transient pushing of the presynaptic boutons with a glass pipette markedly promotes both the evoked release of glutamate and the assembly of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins8,9,10,11,12—as measured by Frster resonance transfer (FRET) and fluorescence lifetime imaging—in rat slice culture preparations13. Both of these effects persisted for more than 20minutes. The increased presynaptic FRET was independent of cytosolic calcium (Ca2+), but dependent on the assembly of SNARE proteins and actin polymerization in the boutons. Notably, a low hypertonic solution of sucrose (20mM) had facilitatory effects on both the FRET and the evoked release without inducing spontaneous release, in striking contrast with a high hypertonic sucrose solution (300mM), which induced exocytosis by itself14. Finally, spine enlargement induced by two-photon glutamate uncaging enhanced the evoked release and the FRET only when the spines pushed the boutons by their elongation. Thus, we have identified a mechanosensory and transduction mechanism15 in the presynaptic boutons, in which the evoked release of glutamate is enhanced for more than 20min.
DOI: 10.1038/s41586-021-04125-7
Source: https://www.nature.com/articles/s41586-021-04125-7
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
