1. Section of Developmental Neurophysiology, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan
2. National Institute for Physiological Sciences, National Institutes of Natural Sciences, Nishigonaka 38, Myodaiji-cho, Okazaki, Aichi, 444-8585, Japan
3. School of Life Science, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan
4. Shimoda Marine Research Center, Graduate School of Life and Environmental Sciences, University of Tsukuba, 5-10-1 Shimoda, Shizuoka 415-0025, Japan
5. Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 6, Higashi 1-1-1, Tsukuba, Ibaraki 305-8566, Japan
6. *These authors contributed equally to this work

Correspondence to: Yasushi Okamura^1,2,3,5 Correspondence and requests for materials should be addressed to Y.O. (Email: yokamura@nips.ac.jp).

Abstract

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^{1, 2, 3} 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.

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