ASIC2 subunits facilitate expression at the cell surface and confer regulation by PSD-95.
ASIC2 subunits facilitate expression at the cell surface and confer regulation by PSD-95.
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DOI：
10.1371/journal.pone.0093797
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Benson CJ
中科院分区：
文献类型：
--
作者：
Harding AM;Kusama N;Hattori T;Gautam M;Benson CJ
酸敏感离子通道（ASIC）是由外周和中枢神经系统内pH值变化激活的Na+通道。ASIC的几种不同亚型联合收割机组合形成三聚体通道，并且它们的性质由它们的亚基组成决定。ASIC 2亚基在整个大脑中广泛表达，在那里它们与它们的伙伴亚基ASIC 1a异源多聚化。然而，ASIC 2对通道的pH敏感性贡献很小，因此其功能尚未得到很好的理解。我们发现，当ASIC 2与ASIC 1a共表达时，它增加了通道的细胞表面水平，并且ASIC 2的基因缺失降低了小鼠海马神经元的酸诱发电流幅度。此外，ASIC 2a与神经元突触支架蛋白PSD-95相互作用，PSD-95降低了含有ASIC 2a的ASIC中的细胞表面表达和电流幅度。PSD-95的过表达也降低了海马神经元的酸诱发电流幅度。这一结果依赖于ASIC 2，因为PSD-95的作用在ASIC 2 −/−神经元中被消除。这些结果支持ASIC 2在ASICs靶向表面膜中的新兴作用，并允许与PSD-95相互作用以调节这些过程。
Acid-sensing ion channels (ASICs) are Na+ channels activated by changes in pH within the peripheral and central nervous systems. Several different isoforms of ASICs combine to form trimeric channels, and their properties are determined by their subunit composition. ASIC2 subunits are widely expressed throughout the brain, where they heteromultimerize with their partnering subunit, ASIC1a. However, ASIC2 contributes little to the pH sensitivity of the channels, and so its function is not well understood. We found that ASIC2 increased cell surface levels of the channel when it is coexpressed with ASIC1a, and genetic deletion of ASIC2 reduced acid-evoked current amplitude in mouse hippocampal neurons. Additionally, ASIC2a interacted with the neuronal synaptic scaffolding protein PSD-95, and PSD-95 reduced cell surface expression and current amplitude in ASICs that contain ASIC2a. Overexpression of PSD-95 also reduced acid-evoked current amplitude in hippocampal neurons. This result was dependent upon ASIC2 since the effect of PSD-95 was abolished in ASIC2−/− neurons. These results lend support to an emerging role of ASIC2 in the targeting of ASICs to surface membranes, and allows for interaction with PSD-95 to regulate these processes.
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DOI：
10.1523/jneurosci.3907-08.2008
发表时间：
2008-12-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Coryell MW;Wunsch AM;Haenfler JM;Allen JE;McBride JL;Davidson BL;Wemmie JA
通讯作者：
Wemmie JA
影响因子：
16.2
作者：
Askwith, CC;Cheng, C;Welsh, MJ
通讯作者：
Welsh, MJ
影响因子：
5.5
作者：
Eshcol, Jayasheel O.;Harding, Anne Marie S.;Benson, Christopher J.
通讯作者：
Benson, Christopher J.
影响因子：
11.4
作者：
Deval, Emmanuel;Noel, Jacques;Lingueglia, Eric
通讯作者：
Lingueglia, Eric
影响因子：
4.8
作者：
Bassilana, F;Champigny, G;Lazdunski, M
通讯作者：
Lazdunski, M