PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current.

The acid-sensing ion channel-3 (ASIC3) is a degenerin/epithelial sodium channel expressed in the peripheral nervous system. Previous studies indicate that it participates in the response to mechanical and painful stimuli, perhaps contributing to mechanoreceptor and/or H+ -gated nociceptor function. ASIC3 subunits contain intracellular N and C termini that may control ...
channel localization and function. We found that a PDZ-binding motif at the ASIC3 C terminus interacts with four different proteins that contain PDZ domains: PSD-95, Lin-7b, MAGI-1b, and PIST. ASIC3 and these interacting proteins were expressed in dorsal root ganglia and spinal cord, and PSD-95 co-precipitated ASIC3 from spinal cord. When expressed in heterologous cells, PSD-95 reduced the amplitude of ASIC3 acid-evoked currents, whereas Lin-7b increased current amplitude. PSD-95 and Lin-7b altered current density by decreasing or increasing, respectively, the amount of ASIC3 on the cell surface. The finding that multiple PDZ-containing proteins bind ASIC3 and can influence its presence in the plasma membrane suggests that they may play an important role in the contribution of ASIC3 to nociception and mechanosensation.
Mesh Terms:
Amino Acid Motifs, Animals, Biotinylation, CHO Cells, COS Cells, Cell Membrane, Cricetinae, DNA, Electrophysiology, Ganglia, Spinal, Green Fluorescent Proteins, Humans, Hydrogen-Ion Concentration, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mice, Microscopy, Fluorescence, Nerve Tissue Proteins, Plasmids, Protein Binding, Protein Structure, Tertiary, Protons, RNA, Messenger, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Sodium Channels, Tissue Distribution, Transfection, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Nov. 05, 2004
Download Curated Data For This Publication
Switch View:
  • Interactions 7