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

Title
Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly
Authors
Kweon, Hae-JinKim, Dong-IlBae, YeonjuPark, Jae-YongSuh, Byung-Chang
DGIST Authors
Suh, Byung-Chang
Issue Date
2016-08
Citation
Scientific Reports, 6, 30684
Type
Article
Article Type
Article
Keywords
BRAIN NA+ CHANNELENDOPLASMIC-RETICULUMSYNAPTIC PLASTICITYPOTASSIUM CHANNELSRETENTION SIGNALG-PROTEINRECEPTORPHSUBUNITEXPORT
ISSN
2045-2322
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.
URI
http://hdl.handle.net/20.500.11750/1542
DOI
10.1038/srep30684
Publisher
Nature Publishing Group
Related Researcher
  • Author Suh, Byung Chang Current Lab
  • Research Interests Molecular mechanisms of epilepsy and sensory pain transmission; Signaling mechanism of ion channel regulation and membrane excitability; 분자전기생리; 간질 및 통증의 분자적 기전 연구
Files:
Collection:
Department of Brain and Cognitive SciencesCurrent Lab1. Journal Articles


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