A new TASK for Dipeptidyl Peptidase-like Protein 6

PLoS One. 2013 Apr 9;8(4):e60831. doi: 10.1371/journal.pone.0060831. Print 2013.


Dipeptidyl Peptidase-like Protein 6 (DPP6) is widely expressed in the brain where it co-assembles with Kv4 channels and KChIP auxiliary subunits to regulate the amplitude and functional properties of the somatodendritic A-current, ISA. Here we show that in cerebellar granule (CG) cells DPP6 also regulates resting membrane potential and input resistance by increasing the amplitude of the IK(SO) resting membrane current. Pharmacological analysis shows that DPP6 acts through the control of a channel with properties matching the K2P channel TASK-3. Heterologous expression and co-immunoprecipitation shows that DPP6 co-expression with TASK-3 results in the formation of a protein complex that enhances resting membrane potassium conductance. The co-regulation of resting and voltage-gated channels by DPP6 produces coordinate shifts in resting membrane potential and A-current gating that optimize the sensitivity of ISA inactivation gating to subthreshold fluctuations in resting membrane potential.

Publication types

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

MeSH terms

  • Action Potentials
  • Animals
  • Cell Line
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Cricetinae
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / genetics
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism*
  • Gene Expression
  • Membrane Potentials
  • Mice
  • Models, Neurological
  • Neurons / physiology
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • RNA Interference
  • Shal Potassium Channels / metabolism


  • Potassium Channels
  • Shal Potassium Channels
  • TASK3 protein, mouse
  • DPP6 protein, mouse
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases