Another Look at Ci-VSP

Abstract

Voltage changes are involved in a range of biological functions including neuronal signal propagation, muscle contraction and T-cell activation. Voltage sensitive proteins respond to the changes in membrane potential via a voltage-sensing domain (VSD). Voltage-gated ion channels use the VSD to open and close a pore domain, which allows for the passive movement of ions down their concentration gradients. The discovery of the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP)(1) opened up a whole new way of looking at voltage sensing. This is the first and only currently known class of protein that has a VSD but no pore. Instead Ci-VSP, and its VSP homologs including fish and frogs, contains a cytoplasmic lipid phosphatase whose activity is regulated by voltage. It is also the only known VSD to work as a monomer instead of in concert with other VSD modules. It still displays similar complex motions as the VSDs from channels which is intriguing. We and others have also shown that lipids play a role in regulating the protein. Even so, many questions remain unanswered regarding how this voltage activated enzyme works. We have taken an interdisciplinary approach including biochemical and electrophysiological approaches to probe the inner workings of VSPs.1. Murata, Y., et al, (2005) Nature 435, 1239-1243.