Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases

Neuropharmacology. 1996;35(7):993-1000. doi: 10.1016/0028-3908(96)00093-7.


The molecular mechanisms underlying the clustering and localization of K+ channels in specific microdomains on the neuronal surface are largely unknown. The Shaker subclass of voltage-gated K+ channel alpha-subunits interact through their cytoplasmic C-terminus with a family of membrane-associated putative guanylate kinases, including PSD-95 and SAP97. We show here that heterologous coexpression of either sap97 or PSD-95 with various Shaker-type subunits results in the coclustering of these proteins with the K+ channels. Mutation of the C-terminal sequence (-ETDV) of the Shaker subunit Kv1.4 abolishes its binding to, and prevents its clustering with, SAP97 and PSD-95. Whereas PSD-95 induces plaque-like clusters of K+ channels at the cell surface; however, SAP97 coexpression results in the formation of large round intracellular aggregates into which both SAP97 and the K+ channel proteins are colocalized. The efficiency of surface clustering by PSD-95 varies with different Shaker subunits: striking Kv1.4 clustering occurs in > 60% of cotransfected cells, whereas Kv1.1 and Kv1.2 form convincing clusters with PSD-95 only in approximately 10% of cells.

MeSH terms

  • Animals
  • COS Cells
  • Guanylate Kinases
  • Kv1.1 Potassium Channel
  • Kv1.4 Potassium Channel
  • Membrane Proteins / metabolism
  • Mutation
  • Nerve Tissue Proteins / metabolism*
  • Nucleoside-Phosphate Kinase / metabolism*
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Precipitin Tests
  • Protein Binding
  • Shaker Superfamily of Potassium Channels
  • Transfection


  • Kv1.4 Potassium Channel
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Shaker Superfamily of Potassium Channels
  • postsynaptic density proteins
  • Kv1.1 Potassium Channel
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases