Molecular determinants for subcellular localization of PSD-95 with an interacting K+ channel

Neuron. 1999 May;23(1):149-57. doi: 10.1016/s0896-6273(00)80761-8.


Ion channels and PSD-95 are colocalized in specific neuronal subcellular locations by an unknown mechanism. To investigate mechanisms of localization, we used biolistic techniques to express GFP-tagged PSD-95 (PSD-95:GFP) and the K(+)-selective channel Kv1.4 in slices of rat cortex. In pyramidal cells, PSD-95:GFP required a single PDZ domain and a region including the SH3 domain for localization to postsynaptic sites. When transfected alone, PSD-95:GFP was present in dendrites but absent from axons. When cotransfected with Kv1.4, PSD-95:GFP appeared in both axons and dendrites, while Kv1.4 was restricted to axons. When domains that mediate the interaction of Kv1.4 and PSD-95 were disrupted, Kv1.4 localized nonspecifically. Our results provide evidence that Kv1.4 itself may determine its subcellular location, while an associated MAGUK protein is a necessary but not sufficient cofactor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / metabolism
  • Dendrites / metabolism
  • Disks Large Homolog 4 Protein
  • Green Fluorescent Proteins
  • In Vitro Techniques
  • Indicators and Reagents
  • Intracellular Signaling Peptides and Proteins
  • Kv1.4 Potassium Channel
  • Luminescent Proteins / genetics
  • Membrane Proteins
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Pyramidal Cells / metabolism
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Subcellular Fractions / metabolism
  • Tissue Distribution / physiology


  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Indicators and Reagents
  • Intracellular Signaling Peptides and Proteins
  • Kcna4 protein, rat
  • Kv1.4 Potassium Channel
  • Luminescent Proteins
  • Membrane Proteins
  • Mpp2 protein, rat
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Recombinant Fusion Proteins
  • postsynaptic density proteins
  • Green Fluorescent Proteins