Document Type

Article

Version Deposited

Published Version

Publication Date

5-7-2018

Publication Title

The Journal of general physiology

DOI

10.1085/jgp.201812064

Abstract

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.

Comments

posted after 6 month embargo per publisher requirements

Creative Commons License

Creative Commons Attribution-Noncommercial-Share Alike 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

Published Citation

Rayaprolu, Vamseedhar et al. “Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.” The Journal of general physiology vol. 150,5 (2018): 683-696. doi:10.1085/jgp.201812064

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