神经科学
兰尼定受体
生物
刺激1
钙信号传导
突触后电位
突触可塑性
突触
作者
Natali L. Chanaday,Elena Nosyreva,Ok Ho Shin,Hua Zhang,İltan Aklan,Deniz Atasoy,Ilya Bezprozvanny,Ege T. Kavalali
出处
期刊:Neuron
[Elsevier]
日期:2021-04-21
卷期号:109 (8)
被引量:11
标识
DOI:10.1016/j.neuron.2021.02.023
摘要
Store-operated calcium entry (SOCE) is activated by depletion of Ca2+ from the endoplasmic reticulum (ER) and mediated by stromal interaction molecule (STIM) proteins. Here, we show that in rat and mouse hippocampal neurons, acute ER Ca2+ depletion increases presynaptic Ca2+ levels and glutamate release through a pathway dependent on STIM2 and the synaptic Ca2+ sensor synaptotagmin-7 (syt7). In contrast, synaptotagmin-1 (syt1) can suppress SOCE-mediated spontaneous release, and STIM2 is required for the increase in spontaneous release seen during syt1 loss of function. We also demonstrate that chronic ER stress activates the same pathway leading to syt7-dependent potentiation of spontaneous glutamate release. During ER stress, inhibition of SOCE or syt7-driven fusion partially restored basal neurotransmission and decreased expression of pro-apoptotic markers, indicating that these processes participate in the amplification of ER-stress-related damage. Taken together, we propose that presynaptic SOCE links ER stress and augmented spontaneous neurotransmission, which may, in turn, facilitate neurodegeneration.
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