Ci-VSP's voltage sensor (blue) regulates a phosphatase domain (green), not a pore domain (pink), as in voltage-gated channels.


The first protein to sense changes in membrane potential but not function as an ion transporter is now identified by Yoshimichi Murata, Hirohide Iwasaki, Mari Sasaki, Yasushi Okamura, and colleagues (National Institutes of Natural Sciences, Aichi, Japan). Activation of this sensor probably induces phosphorylation-based signaling events.The group discovered this sea squirt protein, Ci-VSP, based on its sequence homology with ion channels. But the homology was confined to four transmembrane segments that comprise a voltage sensor. This domain functions just like the voltage sensor domains of channel proteins. Ci-VSP also contains a cytoplasmic phosphatase domain, but lacks a pore domain to transport ions across the plasma membrane.

Using an in vivo bioassay, Okamura's group showed that Ci-VSP changes cellular phosphoinositide concentrations in response to membrane potential changes. “These data provide the first evidence since the Hodgkin-Huxley age that a molecular function other than that of ion channels is regulated by membrane voltage,” he says.

Ci-VSP is expressed in sperm and might function in sperm motility or morphology. The authors' next goal is to identify the natural substrate of Ci-VSP, which they suspect is PIP3, so that they can determine whether membrane hyperpolarization or depolarization activates the enzyme.


Murata, Y., et al.