CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins

Mol Cell Neurosci. 1998 Jun;11(3):161-72. doi: 10.1006/mcne.1998.0679.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Chemistry / physiology
  • COS Cells / chemistry
  • COS Cells / physiology
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Adhesion Molecules, Neuronal
  • Cloning, Molecular
  • Glycoproteins
  • Kidney / chemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Neuropeptides
  • Patch-Clamp Techniques
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Protein Binding / physiology
  • Protein Structure, Tertiary
  • Receptors, AMPA / metabolism
  • Receptors, Kainic Acid / metabolism
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Sequence Homology, Amino Acid
  • Transfection

Substances

  • Carrier Proteins
  • Cell Adhesion Molecules, Neuronal
  • Cipp protein, mouse
  • Glycoproteins
  • Kcnj4 protein, mouse
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • neurexin II
  • neurexophilin
  • neuroligin 2

Associated data

  • GENBANK/AF060539