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A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers

Lipid messengers exert their function on short time scales at distinct subcellular locations, yet most experimental approaches for perturbing their levels trigger cell‐wide concentration changes. Herein, we report on a coumarin‐based photocaging group that can be modified with organelle‐targeting mo...

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Detalles Bibliográficos
Autores principales: Wagner, Nicolai, Stephan, Milena, Höglinger, Doris, Nadler, André
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175159/
https://www.ncbi.nlm.nih.gov/pubmed/30048020
http://dx.doi.org/10.1002/anie.201807497
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author Wagner, Nicolai
Stephan, Milena
Höglinger, Doris
Nadler, André
author_facet Wagner, Nicolai
Stephan, Milena
Höglinger, Doris
Nadler, André
author_sort Wagner, Nicolai
collection PubMed
description Lipid messengers exert their function on short time scales at distinct subcellular locations, yet most experimental approaches for perturbing their levels trigger cell‐wide concentration changes. Herein, we report on a coumarin‐based photocaging group that can be modified with organelle‐targeting moieties by click chemistry and thus enables photorelease of lipid messengers in distinct organelles. We show that caged arachidonic acid and sphingosine derivatives can be selectively delivered to mitochondria, the ER, lysosomes, and the plasma membrane. By comparing the cellular calcium transients induced by localized uncaging of arachidonic acid and sphingosine, we show that the precise intracellular localization of the released second messenger is crucial for the signaling outcome. Ultimately, we anticipate that this new class of caged compounds will greatly facilitate the study of cellular processes on the organelle level.
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spelling pubmed-61751592018-10-15 A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers Wagner, Nicolai Stephan, Milena Höglinger, Doris Nadler, André Angew Chem Int Ed Engl Communications Lipid messengers exert their function on short time scales at distinct subcellular locations, yet most experimental approaches for perturbing their levels trigger cell‐wide concentration changes. Herein, we report on a coumarin‐based photocaging group that can be modified with organelle‐targeting moieties by click chemistry and thus enables photorelease of lipid messengers in distinct organelles. We show that caged arachidonic acid and sphingosine derivatives can be selectively delivered to mitochondria, the ER, lysosomes, and the plasma membrane. By comparing the cellular calcium transients induced by localized uncaging of arachidonic acid and sphingosine, we show that the precise intracellular localization of the released second messenger is crucial for the signaling outcome. Ultimately, we anticipate that this new class of caged compounds will greatly facilitate the study of cellular processes on the organelle level. John Wiley and Sons Inc. 2018-09-03 2018-10-01 /pmc/articles/PMC6175159/ /pubmed/30048020 http://dx.doi.org/10.1002/anie.201807497 Text en © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Communications
Wagner, Nicolai
Stephan, Milena
Höglinger, Doris
Nadler, André
A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers
title A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers
title_full A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers
title_fullStr A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers
title_full_unstemmed A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers
title_short A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers
title_sort click cage: organelle‐specific uncaging of lipid messengers
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175159/
https://www.ncbi.nlm.nih.gov/pubmed/30048020
http://dx.doi.org/10.1002/anie.201807497
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