ASIC2 subunits facilitate expression at the cell surface and confer regulation by PSD-95

Anne Marie S Harding; Nobuyoshi Kusama; Tomonori Hattori; Mamta Gautam; Christopher J Benson

doi:10.1371/journal.pone.0093797

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ASIC2 subunits facilitate expression at the cell surface and confer regulation by PSD-95

Journal article

Open access

Peer reviewed

ASIC2 subunits facilitate expression at the cell surface and confer regulation by PSD-95

Anne Marie S Harding, Nobuyoshi Kusama, Tomonori Hattori, Mamta Gautam and Christopher J Benson

PloS one, Vol.9(4), pp.e93797-e93797

2014

DOI: 10.1371/journal.pone.0093797

PMCID: PMC3974781

PMID: 24699665

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Abstract

Acid-sensing ion channels (ASICs) are Na+ channels activated by changes in pH within the peripheral and central nervous systems. Several different isoforms of ASICs combine to form trimeric channels, and their properties are determined by their subunit composition. ASIC2 subunits are widely expressed throughout the brain, where they heteromultimerize with their partnering subunit, ASIC1a. However, ASIC2 contributes little to the pH sensitivity of the channels, and so its function is not well understood. We found that ASIC2 increased cell surface levels of the channel when it is coexpressed with ASIC1a, and genetic deletion of ASIC2 reduced acid-evoked current amplitude in mouse hippocampal neurons. Additionally, ASIC2a interacted with the neuronal synaptic scaffolding protein PSD-95, and PSD-95 reduced cell surface expression and current amplitude in ASICs that contain ASIC2a. Overexpression of PSD-95 also reduced acid-evoked current amplitude in hippocampal neurons. This result was dependent upon ASIC2 since the effect of PSD-95 was abolished in ASIC2-/- neurons. These results lend support to an emerging role of ASIC2 in the targeting of ASICs to surface membranes, and allows for interaction with PSD-95 to regulate these processes.

Acid Sensing Ion Channels - genetics

Acid Sensing Ion Channels - metabolism

Animals

Cell Membrane - metabolism

CHO Cells

Cricetulus

Disks Large Homolog 4 Protein

Guanylate Kinases - metabolism

Hippocampus - metabolism

Membrane Proteins - metabolism

Mice

Neurons - metabolism

Protein Subunits - genetics

Protein Subunits - metabolism

Details

Title: Subtitle: ASIC2 subunits facilitate expression at the cell surface and confer regulation by PSD-95
Creators: Anne Marie S Harding - Roy J. and Lucille A. Carver College of Medicine
Nobuyoshi Kusama - Roy J. and Lucille A. Carver College of Medicine
Tomonori Hattori - Roy J. and Lucille A. Carver College of Medicine
Mamta Gautam - Roy J. and Lucille A. Carver College of Medicine
Christopher J Benson - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: PloS one, Vol.9(4), pp.e93797-e93797
DOI: 10.1371/journal.pone.0093797
PMID: 24699665
PMCID: PMC3974781
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Grant note: I01 BX000776 / BLRD VA R01 HL076419 / NHLBI NIH HHS DK-25295 / NIDDK NIH HHS
Language: English
Date published: 2014
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984303745002771

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