Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases

Nature. 1995 Nov 2;378(6552):85-8. doi: 10.1038/378085a0.

Abstract

ANCHORING of ion channels at specific subcellular sites is critical for neuronal signalling, but the mechanisms underlying channel localization and clustering are largely unknown (reviewed in ref. 1). Voltage-gated K+ channels are concentrated in various neuronal domains, including presynaptic terminals, nodes of Ranvier and dendrites, where they regulate local membrane excitability. Here we present functional and biochemical evidence that cell-surface clustering of Shaker-subfamily K+ channels is mediated by the PSD-95 family of membrane-associated putative guanylate kinases, as a result of direct binding of the carboxy-terminal cytoplasmic tails to the K+ channel subunits to two PDZ (also known as GLGF or DHR) domains in the PSD-95 protein. The ability of PDZ domains to function as independent modules for protein-protein interaction, and their presence in other junction-associated molecules (such as ZO-1 (ref. 3) and syntrophin), suggest that PDZ-domain-containing polypeptides may be widely involved in the organization of proteins at sites of membrane specialization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • Cell Line
  • Cell Membrane / enzymology
  • Cloning, Molecular
  • Disks Large Homolog 4 Protein
  • Guanylate Kinases
  • Guinea Pigs
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Kv1.4 Potassium Channel
  • Membrane Proteins
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism
  • Nucleoside-Phosphate Kinase / metabolism*
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Protein Binding
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • SAP90-PSD95 Associated Proteins
  • Saccharomyces cerevisiae
  • Tumor Suppressor Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • DLG1 protein, human
  • Disks Large Homolog 4 Protein
  • Dlg1 protein, rat
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • KCNA4 protein, human
  • Kcna4 protein, rat
  • Kv1.4 Potassium Channel
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Recombinant Fusion Proteins
  • SAP90-PSD95 Associated Proteins
  • Tumor Suppressor Proteins
  • postsynaptic density proteins
  • Nucleoside-Phosphate Kinase
  • DLG2 protein, human
  • Guanylate Kinases

Associated data

  • GENBANK/U32376