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Phosphoinositide Phosphatases: Emerging Roles As Voltage Sensors?

Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093

SUMMARY

During a genomic survey of the transparent sea squirt (Ciona intestinalis), Murata et al. discovered a gene that encodes a protein containing homologous sequences to both a CX₅R phosphatase and an ion channel. The authors named the novel protein, C. intestinalis voltage-sensor-containing phosphatase, Ci-VSP. The N terminus of Ci-VSP appears to function as a voltage-gated sensor; the C terminus functions as a phosphoinositide phosphatase. The authors suggest that when the N-terminal voltage sensor is activated, this in turn activates the phosphatase, which converts PI(3,4,5)P₃ to PI(4,5)P₂. Localized changes in membrane PI(4,5)P₂ levels could then serve to either positively or negatively regulate a variety of ion transporters and channels.