The Cytoskeletal Protein α-Actinin Regulates Acid-sensing Ion Channel 1a through a C-terminal Interaction

Mikael K Schnizler; Katrin Schnizler; Xiang-ming Zha; Duane D Hall; John A Wemmie; Johannes W Hell; Michael J Welsh

doi:10.1074/jbc.M805110200

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The Cytoskeletal Protein α-Actinin Regulates Acid-sensing Ion Channel 1a through a C-terminal Interaction

Journal article

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The Cytoskeletal Protein α-Actinin Regulates Acid-sensing Ion Channel 1a through a C-terminal Interaction

Mikael K Schnizler, Katrin Schnizler, Xiang-ming Zha, Duane D Hall, John A Wemmie, Johannes W Hell and Michael J Welsh

The Journal of biological chemistry, Vol.284(5), pp.2697-2705

01/30/2009

DOI: 10.1074/jbc.M805110200

PMCID: PMC2631967

PMID: 19028690

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Abstract

The acid-sensing ion channel 1a (ASIC1a) is widely expressed in central and peripheral neurons where it generates transient cation currents when extracellular pH falls. ASIC1a confers pH-dependent modulation on postsynaptic dendritic spines and has critical effects in neurological diseases associated with a reduced pH. However, knowledge of the proteins that interact with ASIC1a and influence its function is limited. Here, we show that α-actinin, which links membrane proteins to the actin cytoskeleton, associates with ASIC1a in brain and in cultured cells. The interaction depended on an α-actinin-binding site in the ASIC1a C terminus that was specific for ASIC1a versus other ASICs and for α-actinin-1 and -4. Co-expressing α-actinin-4 altered ASIC1a current density, pH sensitivity, desensitization rate, and recovery from desensitization. Moreover, reducing α-actinin expression altered acid-activated currents in hippocampal neurons. These findings suggest that α-actinins may link ASIC1a to a macromolecular complex in the postsynaptic membrane where it regulates ASIC1a activity.

Membrane Transport, Structure, Function, and Biogenesis

Details

Title: Subtitle: The Cytoskeletal Protein α-Actinin Regulates Acid-sensing Ion Channel 1a through a C-terminal Interaction
Creators: Mikael K Schnizler - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
Katrin Schnizler - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
Xiang-ming Zha - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
Duane D Hall - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
John A Wemmie - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
Johannes W Hell - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
Michael J Welsh - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.284(5), pp.2697-2705
DOI: 10.1074/jbc.M805110200
PMID: 19028690
PMCID: PMC2631967
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology
Alternative title: The cytoskeletal protein alpha-actinin regulates acid-sensing ion channel 1a through a C-terminal interaction
Language: English
Date published: 01/30/2009
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
Record Identifier: 9984003455602771

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