title: Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly.
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.
authors.affiliation: Department of Brain &Cognitive Sciences, DGIST, Daegu 42988, Republic of Korea.
authors.forename: Hae-Jin
authors.initials: HJ
authors.lastname: Kweon
authors.affiliation: Department of Brain &Cognitive Sciences, DGIST, Daegu 42988, Republic of Korea.
authors.forename: Dong-Il
authors.initials: DI
authors.lastname: Kim
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Yeonju
authors.initials: Y
authors.lastname: Bae
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Brain &Cognitive Sciences, DGIST, Daegu 42988, Republic of Korea.
authors.forename: Byung-Chang
authors.initials: BC
authors.lastname: Suh
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C568424:ASIC2 protein, human; C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins