Mechanisms and biological role of voltage-regulated phosphatases

Abstract

Voltage sensing nature has long been thought as a trait unique to ion channels. Voltage sensor domain (VSD) is the key module for voltage sensing in voltage-gated ion channels. We have recently identified two novel voltage-sensing proteins that have VSD but lack pore domain. Ci-VSP consists of VSD and phosphatase domain similar to a tumor suppressor enzyme, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Ci-VSP shows robust gating current and voltage-regulated phosphoinositide phosphatase activity. We have also isolated vertebrate orthologs to Ci-VSP and found that they showed similar molecular properties as Ci-VSP including voltage-dependent charge movements and phosphoinositide phosphatase activities. Among vertebrate orthologs, teleost VSP shows robust gating currents in mammalian cells, serving an ideal system to study coupling between VSD and phosphatase domain. Many examples are known in which interaction between distinct modules in a single protein is bidirectional. We found that this was true for VSP, since phosphatase activity modified movement of gating current. In this talk, further findings on the mechanisms of this protein and biological functions will be discussed. [J Physiol Sci. 2007;57 Suppl:S28]