ASIC2a-dependent increase of ASIC3 surface expression enhances the sustained component of the currents.
ASIC2a-dependent increase of ASIC3 surface expression enhances the sustained component of the currents.
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DOI：
10.5483/bmbrep.2016.49.10.057
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发表时间：
2016-10
期刊：
影响因子：
3.8
通讯作者：
Suh BC
中科院分区：
文献类型：
--
作者：
Kweon HJ;Cho JH;Jang IS;Suh BC
酸敏感离子通道（ASIC）是广泛表达于神经系统的质子门控阳离子通道。已知ASIC的质子感测介导疼痛、机械感觉、味觉传导、学习和记忆以及恐惧。在这项研究中，我们研究了ASIC 2a和ASIC 3在异源表达系统中的差异亚细胞定位。虽然ASIC 2a靶向细胞表面本身，但ASIC 3主要积累在ER中，部分表达在质膜中。然而，当ASIC 3与ASIC 2a共表达时，其表面表达显著增加。通过双分子荧光互补（BiFC）分析，我们证实了ASIC 2a和ASIC 3亚基之间的异聚体缔合。此外，我们观察到ASIC 3的ASIC 2a依赖性表面运输显著增强了电流的持续分量。我们的研究表明，ASIC 2a可以通过促进ASIC 3的表面表达，通过异聚体组装，增加膜电导对质子的敏感性。[BMB报告2016; 49（10）：542-547]
Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the nervous system. Proton sensing by ASICs has been known to mediate pain, mechanosensation, taste transduction, learning and memory, and fear. In this study, we investigated the differential subcellular localization of ASIC2a and ASIC3 in heterologous expression systems. While ASIC2a targeted the cell surface itself, ASIC3 was mostly accumulated in the ER with partial expression in the plasma membrane. However, when ASIC3 was co-expressed with ASIC2a, its surface expression was markedly increased. By using bimolecular fluorescence complementation (BiFC) assay, we confirmed the heteromeric association between ASIC2a and ASIC3 subunits. In addition, we observed that the ASIC2a-dependent surface trafficking of ASIC3 remarkably enhanced the sustained component of the currents. Our study demonstrates that ASIC2a can increase the membrane conductance sensitivity to protons by facilitating the surface expression of ASIC3 through herteromeric assembly. [BMB Reports 2016; 49(10): 542-547]