L-Type Voltage-Gated Ca(2+) Channels Regulate Synaptic-Activity-Triggered Recycling Endosome Fusion in Neuronal Dendrites.
L-Type Voltage-Gated Ca(2+) Channels Regulate Synaptic-Activity-Triggered Recycling Endosome Fusion in Neuronal Dendrites.
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DOI：
10.1016/j.celrep.2017.10.105
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发表时间：
2017-11-21
期刊：
影响因子：
8.8
通讯作者：
Kennedy MJ
中科院分区：
文献类型：
--
作者：
Hiester BG;Bourke AM;Sinnen BL;Cook SG;Gibson ES;Smith KR;Kennedy MJ
神经元树突表面蛋白质的库和丰度通过调节再循环内体（RE）与树突质膜的融合来调节。虽然这一过程对神经元功能和可塑性至关重要，但突触活动如何驱动RE融合仍然未被探索。我们展示了一个多步骤的融合机制，需要从不同的来源Ca 2+。NMDA受体Ca 2+启动RE与质膜的融合，而L型电压门控Ca 2+通道（L-VGCC）调节融合的RE是否塌陷到膜中或改革而不将其货物转移到细胞表面。因此，NMDA受体激活触发AMPA型谷氨酸受体运输到树突表面的L-VGCC依赖性的方式。相反，增强L-VGCC增强AMPA受体表面表达时，NMDA受体也活跃。因此，L-VGCC通过门控RE融合模式在调节关键突触蛋白的活性触发的表面表达中发挥作用。神经元树突中的再循环内体（RE）通过调节与树突质膜的融合来调节重要突触分子的丰度。Hiester等人描述了RE融合的多步骤机制，其需要来自不同来源的同时Ca 2+进入：NMDA受体和L型电压门控Ca 2+通道。
The repertoire and abundance of proteins displayed on the surface of neuronal dendrites are tuned by regulated fusion of recycling endosomes (REs) with the dendritic plasma membrane. While this process is critical for neuronal function and plasticity, how synaptic activity drives RE fusion remains unexplored. We demonstrate a multistep fusion mechanism that requires Ca2+ from distinct sources. NMDA receptor Ca2+ initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca2+ channels (L-VGCCs) regulate whether fused REs collapse into the membrane or reform without transferring their cargo to the cell surface. Accordingly, NMDA receptor activation triggered AMPA-type glutamate receptor trafficking to the dendritic surface in an L-VGCC-dependent manner. Conversely, potentiating L-VGCCs enhanced AMPA receptor surface expression only when NMDA receptors were also active. Thus L-VGCCs play a role in tuning activity-triggered surface expression of key synaptic proteins by gating the mode of RE fusion. Recycling endosomes (REs) in neuronal dendrites regulate the abundance of important synaptic molecules by regulated fusion with the dendritic plasma membrane. Hiester et al. describe a multistep mechanism for RE fusion that requires coincident Ca2+ entry from distinct sources: NMDA receptors and L-type voltage-gated Ca2+ channels.
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影响因子：
16.2
作者：
Arendt KL;Zhang Y;Jurado S;Malenka RC;Südhof TC;Chen L
通讯作者：
Chen L
影响因子：
14.8
作者：
Beaudoin, Gerard M. J., III;Lee, Seung-Hye;Arikkath, Jyothi
通讯作者：
Arikkath, Jyothi
影响因子：
5.3
作者：
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通讯作者：
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影响因子：
48
作者：
Grimm, Jonathan B.;English, Brian P.;Lavis, Luke D.
通讯作者：
Lavis, Luke D.
影响因子：
16.2
作者：
Ehlers, MD
通讯作者：
Ehlers, MD