NMDA receptor stimulation induces reversible fission of the neuronal endoplasmic reticulum.
NMDA receptor stimulation induces reversible fission of the neuronal endoplasmic reticulum.
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DOI：
10.1371/journal.pone.0005250
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Toresson H
中科院分区：
文献类型：
--
作者：
Kucharz K;Krogh M;Ng AN;Toresson H
除少数例外，内质网 (ER) 被认为是一个连续的内膜系统，蛋白质和离子可以在其中移动。我们研究了原代培养物和器官切片中海马神经元内质网的动态结构变化。光漂白后的荧光恢复 (FRAP) 用于量化和模拟 ER 结构动力学。通过电子显微镜评估超微结构。在活细胞成像实验中，我们发现，在基础条件下，神经元胞体和树突的ER是连续的。谷氨酸刺激后，内质网光滑、不间断的外观发生了巨大的变化。在神经元损伤出现明显迹象之前，内质网在快速裂变反应中分裂成孤立的囊泡。发现内质网裂变与内质网钙水平无关。除了谷氨酸之外，钙离子载体离子霉素也能够诱导内质网裂变。 N-甲基、D-天冬氨酸 (NMDA) 受体拮抗剂 MK-801 抑制谷氨酸和离子霉素诱导的 ER 裂变。艾芬地尔或激酶抑制剂均不阻断裂变。有趣的是，亚致死的 NMDA 受体刺激导致 ER 快速裂变，然后融合。因此，内质网裂变与细胞损伤或死亡并不严格相关。因此，我们的结果表明，神经元 ER 结构是动态调节的，对蛋白质流动性和 ER 腔钙隧道具有重要影响。
With few exceptions the endoplasmic reticulum (ER) is considered a continuous system of endomembranes within which proteins and ions can move. We have studied dynamic structural changes of the ER in hippocampal neurons in primary culture and organotypic slices. Fluorescence recovery after photobleaching (FRAP) was used to quantify and model ER structural dynamics. Ultrastructure was assessed by electron microscopy. In live cell imaging experiments we found that, under basal conditions, the ER of neuronal soma and dendrites was continuous. The smooth and uninterrupted appearance of the ER changed dramatically after glutamate stimulation. The ER fragmented into isolated vesicles in a rapid fission reaction that occurred prior to overt signs of neuronal damage. ER fission was found to be independent of ER calcium levels. Apart from glutamate, the calcium ionophore ionomycin was able to induce ER fission. The N-methyl, D-aspartate (NMDA) receptor antagonist MK-801 inhibited ER fission induced by glutamate as well as by ionomycin. Fission was not blocked by either ifenprodil or kinase inhibitors. Interestingly, sub-lethal NMDA receptor stimulation caused rapid ER fission followed by fusion. Hence, ER fission is not strictly associated with cellular damage or death. Our results thus demonstrate that neuronal ER structure is dynamically regulated with important consequences for protein mobility and ER luminal calcium tunneling.
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