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Nuclear proton dynamics and interactions with calcium signaling

Biochemical signals acting on the nucleus can regulate gene expression. Despite the inherent affinity of nucleic acids and nuclear proteins (e.g. transcription factors) for protons, little is known about the mechanisms that regulate nuclear pH (pH(nuc)), and how these could be exploited to control g...

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Autores principales: Hulikova, Alzbeta, Swietach, Pawel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915819/
https://www.ncbi.nlm.nih.gov/pubmed/26183898
http://dx.doi.org/10.1016/j.yjmcc.2015.07.003
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author Hulikova, Alzbeta
Swietach, Pawel
author_facet Hulikova, Alzbeta
Swietach, Pawel
author_sort Hulikova, Alzbeta
collection PubMed
description Biochemical signals acting on the nucleus can regulate gene expression. Despite the inherent affinity of nucleic acids and nuclear proteins (e.g. transcription factors) for protons, little is known about the mechanisms that regulate nuclear pH (pH(nuc)), and how these could be exploited to control gene expression. Here, we show that pH(nuc) dynamics can be imaged using the DNA-binding dye Hoechst 33342. Nuclear pores allow the passage of medium-sized molecules (calcein), but protons must first bind to mobile buffers in order to gain access to the nucleoplasm. Fixed buffering residing in the nucleus of permeabilized cells was estimated to be very weak on the basis of the large amplitude of pH(nuc) transients evoked by photolytic H(+)-uncaging or exposure to weak acids/bases. Consequently, the majority of nuclear pH buffering is sourced from the cytoplasm in the form of mobile buffers. Effective proton diffusion was faster in nucleoplasm than in cytoplasm, in agreement with the higher mobile-to-fixed buffering ratio in the nucleus. Cardiac myocyte pH(nuc) changed in response to maneuvers that alter nuclear Ca(2 +) signals. Blocking Ca(2 +) release from inositol-1,4,5-trisphosphate receptors stably alkalinized the nucleus. This Ca(2 +)-pH interaction may arise from competitive binding to common chemical moieties. Competitive binding to mobile buffers may couple the efflux of Ca(2 +)via nuclear pores with a counterflux of protons. This would generate a stable pH gradient between cytoplasm and nucleus that is sensitive to the state of nuclear Ca(2 +) signaling. The unusual behavior of protons in the nucleus provides new mechanisms for regulating cardiac nuclear biology.
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spelling pubmed-49158192016-07-01 Nuclear proton dynamics and interactions with calcium signaling Hulikova, Alzbeta Swietach, Pawel J Mol Cell Cardiol Article Biochemical signals acting on the nucleus can regulate gene expression. Despite the inherent affinity of nucleic acids and nuclear proteins (e.g. transcription factors) for protons, little is known about the mechanisms that regulate nuclear pH (pH(nuc)), and how these could be exploited to control gene expression. Here, we show that pH(nuc) dynamics can be imaged using the DNA-binding dye Hoechst 33342. Nuclear pores allow the passage of medium-sized molecules (calcein), but protons must first bind to mobile buffers in order to gain access to the nucleoplasm. Fixed buffering residing in the nucleus of permeabilized cells was estimated to be very weak on the basis of the large amplitude of pH(nuc) transients evoked by photolytic H(+)-uncaging or exposure to weak acids/bases. Consequently, the majority of nuclear pH buffering is sourced from the cytoplasm in the form of mobile buffers. Effective proton diffusion was faster in nucleoplasm than in cytoplasm, in agreement with the higher mobile-to-fixed buffering ratio in the nucleus. Cardiac myocyte pH(nuc) changed in response to maneuvers that alter nuclear Ca(2 +) signals. Blocking Ca(2 +) release from inositol-1,4,5-trisphosphate receptors stably alkalinized the nucleus. This Ca(2 +)-pH interaction may arise from competitive binding to common chemical moieties. Competitive binding to mobile buffers may couple the efflux of Ca(2 +)via nuclear pores with a counterflux of protons. This would generate a stable pH gradient between cytoplasm and nucleus that is sensitive to the state of nuclear Ca(2 +) signaling. The unusual behavior of protons in the nucleus provides new mechanisms for regulating cardiac nuclear biology. Academic Press 2016-07 /pmc/articles/PMC4915819/ /pubmed/26183898 http://dx.doi.org/10.1016/j.yjmcc.2015.07.003 Text en © 2015 The Authors. Published by Elsevier Ltd. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Hulikova, Alzbeta
Swietach, Pawel
Nuclear proton dynamics and interactions with calcium signaling
title Nuclear proton dynamics and interactions with calcium signaling
title_full Nuclear proton dynamics and interactions with calcium signaling
title_fullStr Nuclear proton dynamics and interactions with calcium signaling
title_full_unstemmed Nuclear proton dynamics and interactions with calcium signaling
title_short Nuclear proton dynamics and interactions with calcium signaling
title_sort nuclear proton dynamics and interactions with calcium signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915819/
https://www.ncbi.nlm.nih.gov/pubmed/26183898
http://dx.doi.org/10.1016/j.yjmcc.2015.07.003
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