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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2697-2705
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number5
DOIs
StatePublished - Jan 30 2009
Externally publishedYes

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Acid Sensing Ion Channels
Actinin
Cytoskeletal Proteins
Neurons
Macromolecular Substances
Dendritic Spines
Application specific integrated circuits
Actin Cytoskeleton
Cations
Actins
Cultured Cells
Brain
Membrane Proteins
Current density
Binding Sites
Cells
Modulation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The cytoskeletal protein α-actinin regulates acid-sensing ion channel 1a through a C-terminal interaction. / Schnizler, Mikael K.; Schnizler, Katrin; Zha, Xiang Ming; Hall, Duane D.; Wemmie, John A.; Hell, Johannes W; Welsh, Michael J.

In: Journal of Biological Chemistry, Vol. 284, No. 5, 30.01.2009, p. 2697-2705.

Research output: Contribution to journalArticle

Schnizler, Mikael K. ; Schnizler, Katrin ; Zha, Xiang Ming ; Hall, Duane D. ; Wemmie, John A. ; Hell, Johannes W ; Welsh, Michael J. / The cytoskeletal protein α-actinin regulates acid-sensing ion channel 1a through a C-terminal interaction. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 5. pp. 2697-2705.
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