Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking ofASIC2b via Heteromeric Assembly

Collection with item attached
2016
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/474214.do
DOI
10.1038/srep30684
Title
Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking ofASIC2b via Heteromeric Assembly
Description
We thank the laboratories of Michael J. Welsh and Takanari Inoue forproviding the plasmids. This work was supported by the National ResearchFoundation of Korea (NRF) grant funded by the Korea government (MSIP)(No. 2016R1A2B4014253), the DGIST R&D Program of the Ministry ofScience, ICT & Future Planning (No. 16-BD-06), and the Korea BrainResearch Institute basic research program funded by the Ministry ofScience, ICT and Future Planning (No. 2231-415).
abstract
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.
provenance
Made available in Cube on 2018-09-28T10:40:11Z (GMT). No. of bitstreams: 0
language
English
author
Kweon, Hae-Jin
Kim, Dong-Il
Bae, Yeonju
Park, Jae-Yong
Suh, Byung-Chang
accessioned
2018-09-28T10:40:11Z
available
2018-09-28T10:40:11Z
issued
2016
citation
Scientific Reports(6)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/474214.do
Funder
미래창조과학부
Funding Program
한국뇌연구원연구운영비지원
Project ID
1711042689
Jurisdiction
Rep.of Korea
Project Name
Hub construction for brain research
rights
openAccess
type
article


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