Voltage-Sensing Phosphatases: Biophysics, Physiology, and Molecular Engineering

Abstract

Voltage-sensing phosphatase (VSP) contains a voltage sensor domain (VSD) similar to that in voltage-gated ion channels, and a phosphoinositide phosphatase region similar to phosphatase and tensin homolog deleted on chromosome 10 (PTEN). The VSP gene is conserved from unicellular organisms to higher vertebrates. Membrane depolarization induces electrical driven conformational rearrangement in the VSD, which is translated into catalytic enzyme activity. Biophysical and structural characterization has revealed details of the mechanisms underlying the molecular functions of VSP. Coupling between the VSD and the enzyme is tight, such that enzyme activity is tuned in a graded fashion to the membrane voltage. Upon VSP activation, multiple species of phosphoinositides are simultaneously altered, and the profile of enzyme activity depends on the history of the membrane potential. VSPs have been the obvious candidate link between membrane potential and phosphoinositide regulation. However, patterns of voltage change regulating VSP in native cells remain largely unknown. This review addresses the current understanding of the biophysical biochemical properties of VSP and provides new insight into the proposed functions of VSP.

Distinct functional properties of two electrogenic isoforms of theSLC34 Na‐Pi cotransporter

“…; Okamura et al. ). Voltage‐sensing phosphatase (VSP) dephosphorylates PI(4,5)P 2 upon membrane depolarization (Murata and Okamura ; Iwasaki et al.…”

“…; Okamura et al. ), thereby inducing its rapid and reversible depletion. Rapamycin‐inducible enzymes are another tool for manipulating phosphoinositide levels.…”

“…Over the last decade, knowledge about the role of PI(4,5)P 2 in the regulation of various types of channels has been obtained through experiments using several molecular tools to manipulate phosphoinositide levels (Balla 2013;Hille et al 2015;Okamura et al 2018). Voltage-sensing phosphatase (VSP) dephosphorylates PI(4,5) P 2 upon membrane depolarization (Murata and Okamura 2007;Iwasaki et al 2008;Okamura et al 2018), thereby inducing its rapid and reversible depletion. Rapamycin-inducible enzymes are another tool for manipulating phosphoinositide levels.…”

Dynamic structural rearrangements and functional regulation of voltage‐sensing phosphatase

“…VSP is conserved from marine invertebrates to humans, where it is expressed in testis, epithelium and neural tissue (Okamura et al . ).…”

“…VSP thus provides a unique example of a membrane protein that performs electrochemical transduction as the single protein. VSP is conserved from marine invertebrates to humans, where it is expressed in testis, epithelium and neural tissue (Okamura et al 2018).…”