Annexin II Light Chain p11 Promotes Functional Expression of Acid-sensing Ion Channel ASIC1a*

  1. John N. Wood,1
  1. Molecular Nociception Group, Department of Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom and the §London Pain Consortium, Department of Biological Sciences, Imperial College, South Kensington Campus, London SW7 2AZ, United Kingdom
  1. 1 To whom correspondence should be addressed. Tel.: 44-20-7679-7800; Fax: 44-20-7679-3519; E-mail: j.wood{at}ucl.ac.uk.

Abstract

Acid-sensing ion channels (ASICs) have been implicated in a wide variety of physiological functions. We have used a rat dorsal root ganglion cDNA library in a yeast two-hybrid assay to identify sensory neuron proteins that interact with ASICs. We found that annexin II light chain p11 physically interacts with the N terminus of ASIC1a, but not other ASIC isoforms. Immunoprecipitation studies confirmed an interaction between p11 and ASIC1 in rat dorsal root ganglion neurons in vivo. Coexpression of p11 and ASIC1a in CHO-K1 cells led to a 2-fold increase in expression of the ion channel at the cell membrane as determined by membrane-associated immunoreactivity and cell-surface biotinylation. Consistent with these findings, peak ASIC1a currents in transfected CHO-K1 cells were up-regulated 2-fold in the presence of p11, whereas ASIC3-mediated currents were unaffected by p11 expression. Neither the pH dependence of activation nor the rates of desensitization were altered by p11, suggesting that its primary role in regulating ASIC1a activity is to enhance cell-surface expression of ASIC1a. These data demonstrate that p11, already known to traffic members of the voltage-gated sodium and potassium channel families as well as transient receptor potential and chloride channels, also plays a selective role in enhancing ASIC1a functional expression.

  • Received June 1, 2005.
  • Revision received September 15, 2005.
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This Article

  1. The Journal of Biological Chemistry 280, 38666-38672.
  1. All Versions of this Article:
    1. M505981200v1
    2. 280/46/38666 (most recent)

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