title: CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins.
abstract: We report a novel multivalent PDZ domain protein, CIPP (for channel-interacting PDZ domain protein), which is expressed exclusively in brain and kidney. Within the brain, the highest CIPP mRNA levels were found in neurons of the cerebellum, inferior colliculus, vestibular nucleus, facial nucleus, and thalamus. Furthermore, we identified the inward rectifier K+ (Kir) channel, Kir4.1 (also called "Kir1.2"), as a cellular CIPP ligand. Among several other Kir channels tested, only the closely related Kir4.2 (or "Kir1.3") also interacted with CIPP. In addition, specific PDZ domains within CIPP associated selectively with the C-termini of N-methyl-D-aspartate subtypes of glutamate receptors, as well as neurexins and neuroligins, cell surface molecules enriched in synaptic membranes. Thus, CIPP may serve as a scaffold that brings structurally diverse but functionally connected proteins into close proximity at the synapse. The functional consequences of CIPP expression on Kir4.1 channels were studied using whole-cell voltage clamp techniques in Kir4.1 transfected COS-7 cells. On average, Kir4.1 current densities were doubled by cotransfection with CIPP.
authors.affiliation: Department of Developmental Neurobiology, Saint Jude Children's Research Hospital, Memphis, Tennessee, 38105, USA. cornelia.kurschner@stjude.org
authors.forename: C
authors.initials: C
authors.lastname: Kurschner
authors.forename: P G
authors.initials: PG
authors.lastname: Mermelstein
authors.forename: W T
authors.initials: WT
authors.lastname: Holden
authors.forename: D J
authors.initials: DJ
authors.lastname: Surmeier
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D019556:COS Cells / Q000737:chemistry / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal; D003001:Cloning, Molecular; D006023:Glycoproteins; D007668:Kidney / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009479:Neuropeptides; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D018091:Receptors, AMPA / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D006023:Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C113147:Cipp protein, mouse; C490969:Kcnj4 protein, mouse; C093175:neurexin II; C112162:neurexophilin; C098003:neuroligin 2