Rayaprolu, VamseedharRoyal, PerrineStengel, KarenSandoz, GuillaumeKohout, Susy C.2018-10-212018-10-212018-05Rayaprolu, Vamseedhar, Perrine Royal, Karen Stengel, Guillaume Sandoz, and Susy C. Kohout. "Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity." Journal of General Physiology 150, no. 5 (May 2018): 683-696. DOI:10.1085/jgp.201812064.0022-1295https://scholarworks.montana.edu/handle/1/14932Multimerization 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.enCC BY-NC-SA: This license lets you remix, tweak, and build upon this work non-commercially, as long as you give credit to the original creator and license your new creations under the identical terms.https://creativecommons.org/licenses/by-nc-sa/4.0/legalcodeArticle