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Optical Control of G-Actin with a Photoswitchable Latrunculin
Actin is one of the most abundant proteins in eukaryotic cells and a key component of the cytoskeleton. A range of small molecules have emerged that interfere with actin dynamics by either binding to polymeric F-actin or monomeric G-actin to stabilize or destabilize filaments or prevent their format...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10370057/ https://www.ncbi.nlm.nih.gov/pubmed/37502978 http://dx.doi.org/10.1101/2023.07.17.549222 |
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author | Vepřek, Nynke A. Cooper, Madeline H. Laprell, Laura Yang, Emily Jie-Ning Folkerts, Sander Bao, Ruiyang Oertner, Thomas G. Pon, Liza A. Zuchero, J. Bradley Trauner, Dirk H. |
author_facet | Vepřek, Nynke A. Cooper, Madeline H. Laprell, Laura Yang, Emily Jie-Ning Folkerts, Sander Bao, Ruiyang Oertner, Thomas G. Pon, Liza A. Zuchero, J. Bradley Trauner, Dirk H. |
author_sort | Vepřek, Nynke A. |
collection | PubMed |
description | Actin is one of the most abundant proteins in eukaryotic cells and a key component of the cytoskeleton. A range of small molecules have emerged that interfere with actin dynamics by either binding to polymeric F-actin or monomeric G-actin to stabilize or destabilize filaments or prevent their formation and growth, respectively. Amongst these, the latrunculins, which bind to G-actin and affect polymerization, are widely used as tools to investigate actin-dependent cellular processes. Here, we report a photoswitchable version of latrunculin, termed opto-latrunculin (OptoLat), which binds to G-actin in a light-dependent fashion and affords optical control over actin polymerization. OptoLat can be activated with 390 – 490 nm pulsed light and rapidly relaxes to the inactive form in the dark. Light activated OptoLat induced depolymerization of F-actin networks in oligodendrocytes and budding yeast, as shown by fluorescence microscopy. Subcellular control of actin dynamics in human cancer cell lines was demonstrated by live cell imaging. Light-activated OptoLat also reduced microglia surveillance in organotypic mouse brain slices while ramification was not affected. Incubation in the dark did not alter the structural and functional integrity of microglia. Together, our data demonstrate that OptoLat is a useful tool for the elucidation of G-actin dependent dynamic processes in cells and tissues. |
format | Online Article Text |
id | pubmed-10370057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-103700572023-07-27 Optical Control of G-Actin with a Photoswitchable Latrunculin Vepřek, Nynke A. Cooper, Madeline H. Laprell, Laura Yang, Emily Jie-Ning Folkerts, Sander Bao, Ruiyang Oertner, Thomas G. Pon, Liza A. Zuchero, J. Bradley Trauner, Dirk H. bioRxiv Article Actin is one of the most abundant proteins in eukaryotic cells and a key component of the cytoskeleton. A range of small molecules have emerged that interfere with actin dynamics by either binding to polymeric F-actin or monomeric G-actin to stabilize or destabilize filaments or prevent their formation and growth, respectively. Amongst these, the latrunculins, which bind to G-actin and affect polymerization, are widely used as tools to investigate actin-dependent cellular processes. Here, we report a photoswitchable version of latrunculin, termed opto-latrunculin (OptoLat), which binds to G-actin in a light-dependent fashion and affords optical control over actin polymerization. OptoLat can be activated with 390 – 490 nm pulsed light and rapidly relaxes to the inactive form in the dark. Light activated OptoLat induced depolymerization of F-actin networks in oligodendrocytes and budding yeast, as shown by fluorescence microscopy. Subcellular control of actin dynamics in human cancer cell lines was demonstrated by live cell imaging. Light-activated OptoLat also reduced microglia surveillance in organotypic mouse brain slices while ramification was not affected. Incubation in the dark did not alter the structural and functional integrity of microglia. Together, our data demonstrate that OptoLat is a useful tool for the elucidation of G-actin dependent dynamic processes in cells and tissues. Cold Spring Harbor Laboratory 2023-07-19 /pmc/articles/PMC10370057/ /pubmed/37502978 http://dx.doi.org/10.1101/2023.07.17.549222 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Vepřek, Nynke A. Cooper, Madeline H. Laprell, Laura Yang, Emily Jie-Ning Folkerts, Sander Bao, Ruiyang Oertner, Thomas G. Pon, Liza A. Zuchero, J. Bradley Trauner, Dirk H. Optical Control of G-Actin with a Photoswitchable Latrunculin |
title | Optical Control of G-Actin with a Photoswitchable Latrunculin |
title_full | Optical Control of G-Actin with a Photoswitchable Latrunculin |
title_fullStr | Optical Control of G-Actin with a Photoswitchable Latrunculin |
title_full_unstemmed | Optical Control of G-Actin with a Photoswitchable Latrunculin |
title_short | Optical Control of G-Actin with a Photoswitchable Latrunculin |
title_sort | optical control of g-actin with a photoswitchable latrunculin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10370057/ https://www.ncbi.nlm.nih.gov/pubmed/37502978 http://dx.doi.org/10.1101/2023.07.17.549222 |
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