Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor

Nature. 2005 Jun 30;435(7046):1239-43. doi: 10.1038/nature03650. Epub 2005 May 18.


Changes in membrane potential affect ion channels and transporters, which then alter intracellular chemical conditions. Other signalling pathways coupled to membrane potential have been suggested but their underlying mechanisms are unknown. Here we describe a novel protein from the ascidian Ciona intestinalis that has a transmembrane voltage-sensing domain homologous to the S1-S4 segments of voltage-gated channels and a cytoplasmic domain similar to phosphatase and tensin homologue. This protein, named C. intestinalis voltage-sensor-containing phosphatase (Ci-VSP), displays channel-like 'gating' currents and directly translates changes in membrane potential into the turnover of phosphoinositides. The activity of the phosphoinositide phosphatase in Ci-VSP is tuned within a physiological range of membrane potential. Immunocytochemical studies show that Ci-VSP is expressed in Ciona sperm tail membranes, indicating a possible role in sperm function or morphology. Our data demonstrate that voltage sensing can function beyond channel proteins and thus more ubiquitously than previously realized.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Ciona intestinalis / enzymology*
  • Ciona intestinalis / genetics
  • Electrophysiology
  • Immunohistochemistry
  • Male
  • Membrane Potentials / physiology*
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Phosphatidylinositols / metabolism*
  • Phosphoric Monoester Hydrolases / chemistry
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Potassium Channels / metabolism
  • Protein Structure, Tertiary
  • Sperm Tail / enzymology
  • Xenopus


  • Phosphatidylinositols
  • Potassium Channels
  • voltage-sensor-containing phosphatase, Ciona intestinalis
  • Phosphoric Monoester Hydrolases