title: The multivalent PDZ domain-containing protein CIPP is a partner of acid-sensing ion channel 3 in sensory neurons.
abstract: Acid-sensing ion channels (ASICs) are cationic channels activated by extracellular pH. They are present in the brain, where they are thought to participate in signal transduction associated with local pH variations, and in sensory neurons, where they have been involved in pain perception associated with tissue acidosis and in mechanoperception. The ASIC3 subunit is mainly expressed in dorsal root ganglion neurons. Its expression is associated with a rapidly inactivating current followed by a slowly activating sustained current thought to be required for the tonic sensation of pain caused by acids. We report here the interaction of this channel subunit with the multivalent PDZ (PSD-95 Drosophila discs-large protein, Zonula occludens protein 1) domain-containing protein CIPP. This interaction requires the C-terminal region of ASIC3 and the fourth PDZ domain of CIPP. Co-expression of CIPP and ASIC3 in COS cells increases the maximal ASIC3 peak current density by a factor of 5 and slightly shifts the pH(0.5) for activation from pH 6.2 to pH 6.4. CIPP mRNA is found at a significant level in the same dorsal root ganglion neuronal cell population that expresses the ASIC3 subunit, i.e. mainly in the small nociceptive neurons. CIPP is thus a scaffolding protein that could both enhance the surface expression of ASIC3 and bring together ASIC3 and functionally related proteins in the membrane of sensory neurons.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UMR6097, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Anzai
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Deval
authors.forename: Lionel
authors.initials: L
authors.lastname: Schaefer
authors.forename: Valerie
authors.initials: V
authors.lastname: Friend
authors.forename: Michel
authors.initials: M
authors.lastname: Lazdunski
authors.forename: Eric
authors.initials: E
authors.lastname: Lingueglia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry*; D004330:Drosophila; D004594:Electrophysiology; D017353:Gene Deletion; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017403:In Situ Hybridization; D007477:Ions; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; C113147:Cipp protein, mouse; D007477:Ions; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase