BMB Rep. 2016; 49(10): 542-547  
ASIC2a-dependent increase of ASIC3 surface expression enhances the sustained component of the currents
Hae-Jin Kweon1, Jin-Hwa Cho2, Il-Sung Jang2 & Byung-Chang Suh1,*
1Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, 2Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea
Correspondence to: Tel: +82-53-785-6123; Fax: +82-53-785-6109; E-mail: bcsuh@
Received: March 16, 2016; Revised: April 8, 2016; Accepted: May 27, 2016; Published online: October 31, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

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.
Keywords: Acid-sensing ion channel, Endoplasmic reticulum, Heteromeric assembly, Membrane protein, Surface trafficking

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