Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly

Hae Jin Kweon, Dong Il Kim, Yeonju Bae, Jae Yong Park, Byung Chang Suh

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9 Citations (Scopus)


Acid-sensing ion channels (ASICs) are proton-activated cation channels that play important roles as typical proton sensors during pathophysiological conditions and normal synaptic activities. Among the ASIC subunits, ASIC2a and ASIC2b are alternative splicing products from the same gene, ACCN1. It has been shown that ASIC2 isoforms have differential subcellular distribution: ASIC2a targets the cell surface by itself, while ASIC2b resides in the ER. However, the underlying mechanism for this differential subcellular localization remained to be further elucidated. By constructing ASIC2 chimeras, we found that the first transmembrane (TM1) domain and the proximal post-TM1 domain (17 amino acids) of ASIC2a are critical for membrane targeting of the proteins. We also observed that replacement of corresponding residues in ASIC2b by those of ASIC2a conferred proton-sensitivity as well as surface expression to ASIC2b. We finally confirmed that ASIC2b is delivered to the cell surface from the ER by forming heteromers with ASIC2a, and that the N-terminal region of ASIC2a is additionally required for the ASIC2a-dependent membrane targeting of ASIC2b. Together, our study supports an important role of ASIC2a in membrane targeting of ASIC2b.

Original languageEnglish
Article number30684
JournalScientific reports
Issue number1
Publication statusPublished - 2016 Aug 26

Bibliographical note

Funding Information:
We thank the laboratories of Michael J. Welsh and Takanari Inoue for providing the plasmids. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2016R1A2B4014253), the DGIST R&D Program of the Ministry of Science, ICT & Future Planning (No. 16-BD-06), and the Korea Brain Research Institute basic research program funded by the Ministry of Science, ICT and Future Planning (No. 2231-415).

Publisher Copyright:
© 2016, The Author(s).

ASJC Scopus subject areas

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