title: ASIC2a-dependent increase of ASIC3 surface expression enhances the sustained component of the currents.
abstract: 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].
authors.affiliation: Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Korea.
authors.forename: Hae-Jin
authors.initials: HJ
authors.lastname: Kweon
authors.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.
authors.forename: Jin-Hwa
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.
authors.forename: Il-Sung
authors.initials: IS
authors.lastname: Jang
authors.affiliation: Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Korea.
authors.forename: Byung-Chang
authors.initials: BC
authors.lastname: Suh
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D018408:Patch-Clamp Techniques; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000378:metabolism
chemical_list: C568265:ASIC2 protein, mouse; C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels