%0 Journal Article %T Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity %A Guillaume %A Guillaume Soz %A Karen %A Karen Stengel %A Kohout %A Perrine %A Perrine Royal %A Rayaprolu %A Royal %A Soz %A Stengel %A Susy C. %A Susy C. Kohout %A Vamseedhar %A Vamseedhar Rayaprolu %J JGP | The Journal of General Physiology %D 2018 %R 10.1085/jgp.201812064 %X Multimerization is a key characteristic of most voltage-sensing proteins. The main exception was thought to be the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP). In this study, we show that multimerization is also critical for Ci-VSP function. Using coimmunoprecipitation and single-molecule pull-down, we find that Ci-VSP stoichiometry is flexible. It exists as both monomers and dimers, with dimers favored at higher concentrations. We show strong dimerization via the voltage-sensing domain (VSD) and weak dimerization via the phosphatase domain. Using voltage-clamp fluorometry, we also find that VSDs cooperate to lower the voltage dependence of activation, thus favoring the activation of Ci-VSP. Finally, using activity assays, we find that dimerization alters Ci-VSP substrate specificity such that only dimeric Ci-VSP is able to dephosphorylate the 3-phosphate from PI(3,4,5)P3 or PI(3,4)P2. Our results indicate that dimerization plays a significant role in Ci-VSP function. %U http://jgp.rupress.org/content/150/5/683