MPS-1 is a K+ channel beta-subunit and a serine/threonine kinase

Nat Neurosci. 2005 Nov;8(11):1503-9. doi: 10.1038/nn1557. Epub 2005 Oct 16.

Abstract

We report the first example of a K+ channel beta-subunit that is also a serine/threonine kinase. MPS-1 is a single-transmembrane domain protein that coassembles with voltage-gated K+ channel KVS-1 in the nervous system of the nematode Caenorhabditis elegans. Biochemical analysis shows that MPS-1 can phosphorylate KVS-1 and other substrates. Electrophysiological analysis in Chinese hamster ovary (CHO) cells demonstrates that MPS-1 activity leads to a significant decrease in the macroscopic current. Single-channel analysis and biotinylation assays indicate that MPS-1 reduces the macroscopic current by lowering the open probability of the channel. These data are consistent with a model that predicts that the MPS-1-dependent phosphorylation of KVS-1 sustains cell excitability by controlling K+ flux.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs / genetics
  • Amino Acid Motifs / physiology
  • Animals
  • Blotting, Western / methods
  • CHO Cells
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Cloning, Molecular / methods
  • Cricetinae
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Immunoprecipitation / methods
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Ion Channel Gating / radiation effects
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Myelin Basic Protein / metabolism
  • Patch-Clamp Techniques / methods
  • Phosphorylation
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Probability
  • Protein Subunits
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Serine
  • Staurosporine / pharmacology
  • Time Factors
  • Transfection / methods

Substances

  • Caenorhabditis elegans Proteins
  • Enzyme Inhibitors
  • MPS-1 protein, C elegans
  • Myelin Basic Protein
  • Potassium Channels
  • Protein Subunits
  • Serine
  • Protein-Serine-Threonine Kinases
  • Staurosporine