Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor

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 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.

Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms

“…Also upstream of the main molecular pathways lies the physiological module driven by the activity of the H ϩ pump. How exactly the membrane voltage is translated into activation of gene expression is not known at present, but mechanisms able to transduce changes in membrane voltages to second messengers are known (Cherubini et al, 2005;Murata et al, 2005). In tail regeneration, results suggest that the H ϩ pump driven proton flux controls regeneration by two mechanisms: control of cell number by means of apoptosis and guidance of axons into the regeneration bud.…”

Functional diversity of potassium channel voltage-sensing domains

“…This calibrated measurement, with different methodologies to measure the number of channels, has been later repeated for Shaker by at least 4 groups, resulting in values of 13.6 e o , 45 12.9 e o , 46 13.6 e o 77 and 13.3. 47 The only other channel, for which a calibrated measurement of the gating charge is available, is the Kv1.2 rat potassium channel.…”

“…When this charge displacement is measured from a large number of channels, it gives rise to a small transient current known as the gating current 73,74 or sensing current in the voltage-sensitive phosphatases. 12,75 The magnitude and time course of gating currents is determined by how much charge is translocated in the opening process and the rates of transitions that move said charges. 73 Since the size of the gating current is also proportional to the number of channels contributing to the measurement, a more interesting measurement is how much charge each channel mobilizes.…”

“…[9][10][11] In fact, VSDs exist as independent gene products, coupled to other kinds of proteins, as demonstrated by the voltage-sensitive phosphatases 12 and can even mediate proton transport, as shown in the voltage-sensitive proton channels. 13,14 As diverse as the functions of VSDs may be, they all work by converting electrostatic energy into conformation changes and it seems that the basic mechanism of voltage sensing is the same.…”

Grafting voltage and pharmacological sensitivity in potassium channels

“…The VSD is formed by four transmembrane segments (S1-S4), and S4 contains 4-8 positively charged residues [4][5][6][7]. However, different from Kv channels, a voltage-gated proton channel Hv1 consists of two VSDs, and a voltage sensor-containing phosphatase Ci-VSP contains one VSD, suggesting that a single VSD can sense changes in the membrane potential and function independently [8][9][10]. Discoveries of voltage-sensing proteins with less than four VSDs raised a fundamental question: how many VSDs are necessary to confer the voltage sensitivity in one Kv channel [11]?…”