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

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 Kinase, Kv1.1 Potassium Channel, Kv1.4 Potassium Channel, Membrane Proteins, Mutation, Nerve Tissue Proteins, Nucleoside-Phosphate Kinase, Potassium Channels, Potassium Channels, Voltage-Gated, Precipitin Tests, Protein Binding, Shaker Superfamily of Potassium Channels, Transfection
Neuropharmacology
Date: Jan. 01, 1996
Download Curated Data For This Publication
6473
Switch View:
  • Interactions 3