RGD Reference Report - Regulation of sensory neuron-specific acid-sensing ion channel 3 by the adaptor protein Na+/H+ exchanger regulatory factor-1. - Rat Genome Database

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Regulation of sensory neuron-specific acid-sensing ion channel 3 by the adaptor protein Na+/H+ exchanger regulatory factor-1.

Authors: Deval, E  Friend, V  Thirant, C  Salinas, M  Jodar, M  Lazdunski, M  Lingueglia, E 
Citation: Deval E, etal., J Biol Chem. 2006 Jan 20;281(3):1796-807. Epub 2005 Oct 17.
RGD ID: 1581392
Pubmed: PMID:16234233   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M509669200   (Journal Full-text)

Acid-sensing ion channels (ASICs) are cationic channels activated by extracellular protons. The ASIC3 subunit is largely expressed in the peripheral nervous system, where it contributes to pain perception and to some aspects of mechanosensation. We report here a PDZ-dependent and protein kinase C-modulated association between ASIC3 and the Na+/H+ exchanger regulatory factor-1 (NHERF-1) adaptor protein. We show that NHERF-1 and ASIC3 are co-expressed in dorsal root ganglion neurons. NHERF-1 enhances the ASIC3 peak current in heterologous cells, including F-11 dorsal root ganglion cells, by increasing the amount of channel at the plasma membrane. Perhaps more importantly, we show that the plateau current of ASIC3 can be dramatically increased (10-30-fold) by association with NHERF-1, leading to a significant sustained current at pH 6.6. In the presence of NHERF-1, the ASIC3 subcellular localization is modified, and the channel co-localizes with ezrin, a member of the ezrin-radixin-moesin family of actin-binding proteins, providing the first direct link between ASIC3 and the cortical cytoskeleton. Given the importance of the ASIC3 sustained current in nociceptor excitability, it is likely that NHERF-1 participates in channel functions associated with nociception and mechanosensation.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Asic3Ratperinuclear region of cytoplasm  IDA  RGD 

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Asic3  (acid sensing ion channel subunit 3)
Nherf1  (NHERF family PDZ scaffold protein 1)
Nherf2  (NHERF family PDZ scaffold protein 2)


Additional Information