Cargando…

Reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization

Voltage-sensing phosphatases (VSPs) cleave both 3- and 5-phosphates from inositol phospholipids in response to membrane depolarization. When low concentrations of Ciona intestinalis VSP are expressed in Xenopus laevis oocytes, the 5-phosphatase reaction can be observed during large membrane depolari...

Descripción completa

Detalles Bibliográficos
Autores principales: Kruse, Martin, Kohout, Susy C., Hille, Bertil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363406/
https://www.ncbi.nlm.nih.gov/pubmed/30622132
http://dx.doi.org/10.1085/jgp.201812260
_version_ 1783393096733556736
author Kruse, Martin
Kohout, Susy C.
Hille, Bertil
author_facet Kruse, Martin
Kohout, Susy C.
Hille, Bertil
author_sort Kruse, Martin
collection PubMed
description Voltage-sensing phosphatases (VSPs) cleave both 3- and 5-phosphates from inositol phospholipids in response to membrane depolarization. When low concentrations of Ciona intestinalis VSP are expressed in Xenopus laevis oocytes, the 5-phosphatase reaction can be observed during large membrane depolarizations. When higher concentrations are expressed, the 5-phosphatase activity is observed with smaller depolarizations, and the 3-phosphatase activity is revealed with strong depolarization. Here we ask whether this apparent induction of 3-phosphatase activity is attributable to the dimerization that has been reported when VSP is expressed at higher concentrations. Using a simple kinetic model, we show that these enzymatic phenomena can be understood as an emergent property of a voltage-dependent enzyme with invariant substrate selectivity operating in the context of endogenous lipid-metabolizing enzymes present in oocytes. Thus, a switch of substrate specificity with dimerization need not be invoked to explain the appearance of 3-phosphatase activity at high VSP concentrations.
format Online
Article
Text
id pubmed-6363406
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-63634062019-08-04 Reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization Kruse, Martin Kohout, Susy C. Hille, Bertil J Gen Physiol Research Articles Voltage-sensing phosphatases (VSPs) cleave both 3- and 5-phosphates from inositol phospholipids in response to membrane depolarization. When low concentrations of Ciona intestinalis VSP are expressed in Xenopus laevis oocytes, the 5-phosphatase reaction can be observed during large membrane depolarizations. When higher concentrations are expressed, the 5-phosphatase activity is observed with smaller depolarizations, and the 3-phosphatase activity is revealed with strong depolarization. Here we ask whether this apparent induction of 3-phosphatase activity is attributable to the dimerization that has been reported when VSP is expressed at higher concentrations. Using a simple kinetic model, we show that these enzymatic phenomena can be understood as an emergent property of a voltage-dependent enzyme with invariant substrate selectivity operating in the context of endogenous lipid-metabolizing enzymes present in oocytes. Thus, a switch of substrate specificity with dimerization need not be invoked to explain the appearance of 3-phosphatase activity at high VSP concentrations. Rockefeller University Press 2019-02-04 /pmc/articles/PMC6363406/ /pubmed/30622132 http://dx.doi.org/10.1085/jgp.201812260 Text en © 2019 Kruse et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Kruse, Martin
Kohout, Susy C.
Hille, Bertil
Reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization
title Reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization
title_full Reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization
title_fullStr Reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization
title_full_unstemmed Reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization
title_short Reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization
title_sort reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363406/
https://www.ncbi.nlm.nih.gov/pubmed/30622132
http://dx.doi.org/10.1085/jgp.201812260
work_keys_str_mv AT krusemartin reinterpretationofthesubstratespecificityofthevoltagesensingphosphataseduringdimerization
AT kohoutsusyc reinterpretationofthesubstratespecificityofthevoltagesensingphosphataseduringdimerization
AT hillebertil reinterpretationofthesubstratespecificityofthevoltagesensingphosphataseduringdimerization