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bioRxiv · 10.1101/2022.02.21.480923

Next Generation Opto-Jasplakinolides Enable Local Remodeling of Actin Networks

Küllmer, F.·Veprek, N. A.·Borowiak, M.·Nasufovic, V.·Barutzki, S.·Thorn-Seshold, O.·Arndt, H.-D.·Trauner, D. H.
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Abstract

The natural product jasplakinolide is a widely used tool compound to stabilize F-actin and influence actin dynamics. We have previously introduced photoswitchable jasplakinolides (optojasps) that are activated with violet light and deactivated with blue light. Based on insights from cryo-electron microscopy and structure-activity relationship (SAR) studies, we now developed a new generation of functionally superior optojasps that are better suited for biological investigations. These compounds are procured through chemical total synthesis and feature rationally designed red-shifted azobenzene photoswitches. Our new optojasps can be activated with longer wavelengths in the visible range (e.g. 440-477 nm) and rapidly return to their inactive state through thermal relaxation. This has enabled the reversible control of F-actin dynamics, as shown through live-cell imaging and cell migration, as well as cell proliferation assays. Brief sub-cellular activation with blue-green light resulted in highly localized F-actin clusters that gradually dissolved in the dark. Our light-responsive tools can be useful in diverse fields to study actin dynamics with outstanding spatiotemporal precision. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/480923v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1883e3corg.highwire.dtl.DTLVardef@1ae0c4borg.highwire.dtl.DTLVardef@1a92f8forg.highwire.dtl.DTLVardef@718d87_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Küllmer, F., Veprek, N. A., Borowiak, M., Nasufovic, V., Barutzki, S., Thorn-Seshold, O., Arndt, H.-D., Trauner, D. H.. 2022-02-21. Next Generation Opto-Jasplakinolides Enable Local Remodeling of Actin Networks. https://doi.org/10.1101/2022.02.21.480923

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